Over-The-Counter Human Drugs; Labeling Requirements
Federal RegisterMar 17, 1999
Ask Donna
What actually matters in this document.
Text
SUMMARY: The Food and Drug Administration (FDA) is issuing a final rule
establishing a standardized format and standardized content
requirements for the labeling of over-the-counter (OTC) drug products.
This final rule is intended to assist consumers in reading and
understanding OTC drug product labeling so that consumers may use these
products safely and effectively. This final rule will require all OTC
drug products to carry the new, easy-to-read format and the revised
content requirements within prescribed implementation periods.
DATES:
Effective Date: April 16, 1999.
Compliance Dates: For compliance dates see section V of the
SUPPLEMENTARY INFORMATION section of this document.
FOR FURTHER INFORMATION CONTACT: Debra L. Bowen, Food and Drug
Administration, Center for Drug Evaluation and Research (HFD-560), 5600
Fishers Lane, Rockville, MD 20852, 301-827-2222, or email
``[email protected]''.
SUPPLEMENTARY INFORMATION:
I. Background
In the Federal Register of February 27, 1997 (62 FR 9024), FDA
proposed to establish a standardized format for the labeling of OTC
drug products that included: (1) Specific headings and subheadings
presented in a standardized order, (2) standardized graphical features
such as Helvetica type style and the use of ``bullet points'' to
introduce key information, and (3) minimum standards for type size and
spacing. The proposal included an extensive list of ``connecting
terms'' that manufacturers may omit from product labeling, and an
expanded list of ``interchangeable terms'' to facilitate the use of
more concise and easy to understand language in OTC drug product
labeling. The agency also proposed to amend several specific warnings,
including the required pregnancy-nursing warning, the ``keep out of
reach of children'' warning, and the accidental overdose/ingestion
warnings, to make these warnings as direct and understandable as
possible. Finally, the agency proposed to preempt State and local rules
that establish different requirements than those in the proposed rule,
to promote a national, standardized format for all OTC drug product
labeling.
The agency discussed at length its basis for proposing to improve
labeling design (62 FR 9024 at 9027 through 9031). The agency stated
that a standardized labeling format would significantly improve
readability by familiarizing consumers with the types of information in
OTC drug product labeling and the location of that information. In
addition, a standardized appearance and standardized content, including
various ``user-friendly'' visual cues, would help consumers locate and
read important health and safety information and allow quick and
effective product comparisons, thereby helping consumers to select the
most appropriate product.
The agency reviewed literature studies that confirmed that OTC drug
product labeling often lacks the graphical features and visual cues
needed to ensure readability and comprehension. These and other studies
recommended ways to make labeling easier to read and understand,
described the importance of adherence to directions for use, and
reported on a number of preventable adverse drug reactions from OTC
drug products (see 62 FR 9024 at 9027 and 9028).
The agency also has benefitted significantly in this proceeding
from the experience it gained in redesigning food labeling under the
Nutrition Labeling and Education Act of 1990 (NLEA) (Pub. L. 101-535,
November 8, 1990). The agency's required nutrition labeling panel
(Sec. 101.9 (21 CFR 101.9)) provides a standardized graphic
presentation for food nutrients, allowing consumers to judge the
significance of the level of a particular nutrient in a product in the
context of a total daily diet. Since its implementation in 1993, the
agency has received praise from consumers and nutritionists, noting the
impact and utility of the standardized food label.
The agency provided over 7 months for interested persons to comment
on the OTC labeling proposal, which included an extension of the
comment period from June 27, 1997, to October 6, 1997, published in the
Federal Register on June 19, 1997 (62 FR 33379). In addition, the
agency solicited public comment on two labeling studies it conducted.
In the Federal Register of December 30, 1997 (62 FR 67770), the agency
sought comment (until February 13, 1998) on a study entitled
``Evaluation of Revised Formats for Over-the-Counter (OTC) Drugs''
(Study B). Study B consisted of a survey of more than 900 respondents
to evaluate consumer preference for design variations in drug labeling
formats. In the Federal Register of February 13, 1998 (63 FR 7331), the
agency solicited comment (until March 30, 1998) on a second study
entitled ``Evaluation of Proposed Over-the-Counter (OTC) Label Format
Comprehension Study'' (Study A). Study A consisted of a survey of more
than 1,200 consumers on the influence of variations in labeling formats
on the communication of directions for use and required warnings.
In response to the proposed rule and the publication of Studies A
and B, the agency received more than 1,800 comments from health
professionals and students, professional organizations, trade
associations, manufacturers, consumers, and consumer organizations. An
overwhelming majority of the comments supported the agency's initiative
to standardize the format of OTC drug product labeling and to make the
labeling easier to read and understand by requiring a minimum type
size, user-friendly headings, and other well-accepted visual cues.
However, a number of specific points in the proposal generated
extensive, and sometimes divergent, comment: (1) Whether pharmacists,
nurses, or other health professionals should be specifically referenced
in certain of the proposed headings; (2) an appropriate minimum type
size for the required labeling information; (3) application of the
proposed labeling format to products traditionally marketed in small
containers and products marketed as both drugs and cosmetics; and (4)
continued reference to Poison Control Centers in the required
accidental ingestion warning. These and other comments are addressed at
length in section IV of this document.
The agency has considered the information presented in the proposed
rule, the comments received, the results from Studies A and B, and all
other relevant information, and concludes that the standardized format
and content requirements for OTC drug product labeling, as set forth in
this final rule, will enable consumers to better read and understand
the information presented and apply this
[[Page 13255]]
information to the safe and effective use of OTC drug products.
As discussed in the proposed rule, research on reading behavior and
document simplification shows that the use of less complex terminology,
presented in shorter sentences with an organized or ``chunked''
structure, is likely to improve consumer processing of the information
(Refs. 1, 2, and 3). Research also shows that consumers are more likely
to engage in behavior that they believe they can successfully complete
than in behavior that appears overwhelming (Ref. 4) or that presents a
``cognitive load,'' such as the task of reading densely worded consumer
information (Ref. 5).
The new OTC drug product labeling is expected to decrease
``cognitive load'' by, among other things, decreasing the memory
demands necessary for processing the information. This, in turn, will
allow consumers to process the information faster. In addition, the new
format offers a more structured, organized, and compact presentation,
which places fewer and less imposing processing demands on the reader.
The consumer's self-perceived ability to read the labeling will
increase significantly and, thereby, result in an improved overall
understanding of the information presented. Finally, the new labeling
is expected to provide clear signals regarding important information,
leading to increased processing and communication of this information.
II. Prototype Labeling Based on This Final Rule
An outline of the various labeling provisions for OTC drug products
is shown below:
BILLING CODE 4160-01-F
[GRAPHIC] [TIFF OMITTED] TR17MR99.000
BILLING CODE 4160-01-C
[[Page 13256]]
An example of labeling for a single ingredient antihistamine OTC
drug product, annotated for illustrative purposes, is shown below. FDA
recommends use of the type style and font sizes shown below:
[GRAPHIC] [TIFF OMITTED] TR17MR99.001
An example of labeling for an antacid OTC drug product, applying
the modified, small package labeling provisions in this final rule and
annotated for illustrative purposes, is shown below. FDA recommends use
of the type style and font sizes shown below:
[GRAPHIC] [TIFF OMITTED] TR17MR99.002
BILLING CODE 4160-01-C
[[Page 13257]]
Examples of prototype OTC drug product labeling are attached in
Appendix A of this document. The information in these examples is
presented using ordinary package sizes for these types of products.
These examples are for illustrative purposes only and are not intended
to depict specific products. Some are based on proposed monograph
requirements only. Example 1 depicts sample labeling for a single
ingredient antihistamine product, using the format and content
provisions set forth in this final rule. Example 2 depicts labeling for
a combination cough/cold product using the format and content
provisions set forth in this final rule. Example 3 demonstrates how the
same information shown in Example 2 can be presented directly on the
package label for an 8-ounce bottle of syrup, using the small package
modifications specified in the final rule. Example 4 depicts a
toothpaste that is marketed as a standing tube without an outer carton,
using the format and content provisions set forth in this final rule.
Example 5 demonstrates labeling for a drug product that is also
marketed for cosmetic uses using the format and content provisions set
forth in this final rule. Example 5 also demonstrates an acceptable
``similar enclosure'' to a box. Example 6 depicts labeling for a
topical acne product that is marketed in a tube and packaged in a
carton with a riser, in order to provide additional labeling space.
Example 7 depicts labeling for an antacid product, applying the small
package modifications.
III. Summary of Studies A and B
Studies A and B tested whether the proposed format improves the
readability and understandability of OTC drug product labeling and
investigated consumer preference for certain format variations. The
studies confirm that the new labeling format will increase
communication of OTC drug product information.
A. Study A
Study A examined the influence of labeling formats and the use of
selective highlighting on the communication of directions for use and
warnings. The study examined two levels of four independent variables
in a factorial design: (1) Labeling format (prototypical existing
format versus proposed new format), (2) drug type (cough-cold versus
pain reliever), (3) the use of highlighting (more versus less emphasis
on graphic design features), and (4) consumer attention (divided versus
focused). Highlighting, label format, and drug type were varied in the
design of the sample product label. Attention (focused or divided) was
varied through instructions given to the respondents. Study
participants were asked to read a food label, then a drug label to test
for divided and focused attention. Half of the participants were told
they would be asked questions about both labels (divided attention);
the other half were told they would be tested only on the drug label
(focused attention) and that the food label was to serve only as
reading practice.
The study included 1,202 respondents in 8 geographically
distributed shopping malls in the United States, with approximately
equal numbers of respondents from each location. Respondents were asked
to evaluate the presentation of label information on one OTC drug
sample and were asked questions about the labeling to determine their
knowledge, opinions, and willingness to read the labeling.
Dependent measures were analyzed using a general linear model
analysis of variance. The study demonstrated that the proposed new
format took less time and was easier to read and understand than a
product that did not follow the new format. Study respondents indicated
a general preference for the proposed format and, when their attention
was divided, respondents felt more confident in their ability to use
the proposed format labeling. When more graphical design features were
used, respondents who were instructed to focus on the labeling made
more correct product use decisions, compared to respondents whose
attention was divided. There were no conditions under which a product
with an existing labeling format outperformed the proposed new format.
The results from Study A suggest that consumers who are presented
with the new labeling format will be: (1) More confident in their
ability to use the information in the labeling, and (2) better able to
make correct product use decisions.
B. Study B
This study investigated consumer preferences for format and
graphical design variations. The study examined two levels of each of
four independent variables in a factorial design: (1) The order of the
``Warning(s)'' and ``Direction(s)'' section (i.e., warnings before
directions or warnings after directions), (2) the placement of the
``Active ingredients'' section at the top of the labeling versus
bottom, (3) the use of a title as an introduction to the required
information (``Medication Facts'' versus no title), and (4) the use of
dividing lines between sections (thick versus thin lines).
This study included 904 respondents in 8 geographically distributed
shopping malls in the United States, with approximately equal numbers
of respondents from each location. The respondents were asked to
evaluate 16 labeling variations of either a sample cough-cold or
sunscreen drug product. The respondents were also asked to rank the
randomly ordered labels from most to least preferred, to specify the
reasons for their first and second choices, and to rate a current OTC
drug product that did not follow the new format.
The study showed that the presence of a title was the most
important factor in determining preference, as participants were more
likely to choose labeling with a title than without. When asked why
they preferred the label ranked as number one, the respondents
indicated that it: (1) Was easy to read, and (2) begins with
``Medication Facts.''
The agency performed a primary conjoint analysis on the preference
rankings. A conjoint analysis simultaneously weighs multiple variables
and allows for a determination of the relative importance of each
particular attribute of a variable, in addition to the level at which
each attribute is preferred (SPSS Categories, 1994). Results indicated
that, of the four factors examined, title had the greatest impact on
rankings, with a utility range from -1.83 for no title and +1.83 for
the ``Medication Facts'' title. In this primary analysis, the effect of
the other three variables was not significant.
The agency also performed a secondary analysis of the data, to look
at differences between variables, independent of context. For labeling
with a title, the mean ranks were 6.67 and 10.33 (Z=-20, SD=1.95,
p1
----------------------------------------------------------------------------------------------------------------
Annual
21 CFR Section No. of Frequency per Total Annual Hours per Total Hours
Respondents Response Responses Response
----------------------------------------------------------------------------------------------------------------
201.662 400 31.43 12,573 4 50,292
201.66 400 66.8 26,737 2.5 66,842
201.66(c) and (d)2 61 8.5 522 2 1,044
201.66(e) 25 4 100 24 2,400
Total 120,578
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operation and maintenance costs associated with this collection of
information.
\2\ One-time burden.
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
A. Background and Summary
FDA has examined the impacts of the final rule under Executive
Order 12866, the Regulatory Flexibility Act (5 U.S.C. 601-612), and the
Unfunded Mandates Reform Act (2 U.S.C. 1501 et seq.). 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 impact on a substantial
number of small entities, an agency must analyze regulatory options
that would minimize any significant impact of the rule on small
entities. Title II of the Unfunded Mandates Reform Act requires that
agencies prepare a written assessment and economic analysis before
proposing any rule that may result in an expenditure in any 1 year by
State, local, and tribal governments, in the aggregate, or by the
private sector, of $100 million (adjusted annually for inflation).
The agency believes that this final rule is consistent with the
principles set out in the Executive Order and in these two statutes.
The final rule is a significant regulatory action as defined by the
Executive Order due to the novel policy issues it raises. It is also an
economically significant regulatory action because of its substantial
benefits. With respect to the Regulatory Flexibility Act, the following
analysis constitutes the agency's Final Regulatory Flexibility
Analysis. Because the rule does not impose any mandates on State,
local, or tribal governments, or the private sector, that will result
in an expenditure in any 1 year of $100 million or more, FDA is not
required to perform a cost-benefit analysis according to the Unfunded
Mandates Reform Act.
The standardized format and easier-to-read labels established by
this rule will have a positive effect on the nation's public health by
enhancing the ability of consumers to find, read, and understand
important safety and use information. The expected benefits of the rule
will include: (1) Improved drug effectiveness for labeled indications,
(2) reduced adverse drug reactions, and (3) more efficient consumer
search activities. The health benefits that will result from improved
drug effectiveness could not be quantified, but FDA believes that they
are substantial. With respect to the anticipated reduction in adverse
drug events, the agency finds that if the rule prevents just 5 percent
of the hospitalizations associated with the unintended consequences of
self-medication, the economic savings could be $39 million annually in
direct benefits and $52 million annually from indirect benefits. In
addition, by reducing consumer search time, the uniform format could
lead to consumer time savings valued at from $19 million to $38 million
per year. The total benefits of this rule range from $110.5 million to
$129.6 million per year.
The costs of the product redesign and relabeling imposed by this
rule will be incurred by the manufacturers of OTC drug products. FDA
estimates that the required labeling redesign will cost about $19.4
million. In addition, the minimum print size and other format changes
will require a small percentage of products (estimated at 6.4 percent)
to increase the size of their label and/or package. These size-related
adjustments will add about $38 million in one-time costs and $11.5
million in annually recurring costs. Overall, therefore, the agency
estimates that the one-time costs of this rule will amount to about $58
million and the annual recurring costs about $11.5 million.
B. Benefits of Regulation
The purpose of this final rule is to establish a standardized
format for the labeling of all OTC drug products so that the labeling
will be easier to read and understand, and will provide consistent
information in like situations. Thus, the final rule will enhance the
safe and effective use of OTC drug products by improving the ability of
consumers to find, read, and understand important safety and use
information. As discussed in section III.A of this document, the agency
conducted a study (Study A) to examine the influence on comprehension
of the new versus the previously used OTC labeling format. That study
supports the conclusion that the new format will take less time to read
and will help consumers make a greater number of correct product use
decisions when such decisions require a simple search for information
in the product labeling. The study found that individuals like a format
with strong visual cues and consider information easier to use when
presented in easy to read ``chunks.'' Especially when attention is
divided, individuals felt more confident in their ability to use such a
format.
[[Page 13277]]
Both the variability and the presentation of existing OTC drug
product labeling make it difficult for consumers to select the most
appropriate OTC drug product and to use the product safely and
effectively. For consumers to gain the greatest benefit from these
products, relevant information must be easy to find, readable, readily
understood, noted, and acted upon. Despite the critical importance of
safety and use information, OTC drug product labeling is often printed
in small type with a crowded layout and minimal white space. Although
the OTC drug industry has developed voluntary labeling standards
encouraging a minimum 6-point type size, many OTC drug product labels
fail to meet this standard. Moreover, the placement of the information
varies, making it harder for consumers to find and compare similar
information on competing products.
The revised labeling will produce at least three important
benefits: (1) The new label will enhance the therapeutic value of OTC
drug products by helping consumers select appropriate products and
adhere to proper dosage regimens; (2) consumers will find it easier to
avoid ingredients or products that in some circumstances cause adverse
events such as allergic reactions, adverse drug interactions, or other
unintended outcomes, ranging from minor discomfort to hospitalization;
and (3) consumers will increase the economic efficiency of their OTC
drug purchases by more quickly locating and identifying key elements of
product information, such as appropriate ingredients, uses, and
warnings.
1. Improved Product Selection and Use
The number of consumers relying on self-diagnosis and self-
treatment has increased rapidly over the past decade, due in part to
the rising cost of health care and the increasing number of drug
products switched from prescription to OTC status. Consumers, however,
are faced with a growing number of choices for purchase decisions and
often find it difficult to determine the product that is best for their
particular condition. The absence of uniform and easily readable
product information complicates product comparisons and can result in
less than optimal health outcomes. Moreover, even informed product
selections can produce disappointing results if directions for use are
misread. Inappropriate product selections or illegible dosage
directions can postpone relief from aches or pains, or permit other
discomforts to persist longer than necessary. Study A suggests that the
standardized labeling format will reduce such incorrect product use
decisions. Although FDA cannot quantify the value of the health
improvements that would result, the agency is confident that the more
informed OTC drug selection and use produced by this rule will increase
consumer satisfaction and, at times, reduce health care costs for
additional or supplemental medications, doctor visits, and
hospitalizations.
2. Savings From Reduced Adverse Drug Reactions
Although adverse events associated with some OTC drug products are
not systematically tracked and recorded, substantial documentation does
exist for the more serious events. Numerous studies in the literature
have documented drug-related hospitalizations (60 FR 44182 at 44232,
August 24, 1995). One comprehensive review of 36 articles focused
specifically on adverse drug reactions (ADR's) as the primary cause of
hospitalization. This study counted the number of events attributed to
the unintended consequences of drug therapy, excluding admissions due
to overdose, intentional poisoning, attempted suicides, drug abuse or
intoxication, and found that the percentage of hospitalizations due to
ADR's ranged from 0.2 to 22 percent, with a mean of 5.5 percent (Ref.
16). Of those studies that distinguished between prescription and OTC
drugs, the reported OTC share ranged from between 4 (Ref. 17) and 18
percent (Refs. 18 and 19). Thus, FDA estimates that unintended OTC
drug-related hospitalizations may account for about 0.55 percent (5.5
percent x 10 percent), or 170,500 of the nation's 31 million annual
hospital admissions. Investigators have determined that between 48 and
55 percent of all hospital admissions related to adverse reactions are
preventable (60 FR 44182 at 44232). (A recent study of in-hospital
adverse drug reactions also found that almost 50 percent were
preventable.) (Ref. 20). Consequently, on the assumption that 50
percent of the hospitalizations attributable to OTC drug adverse
reactions are preventable and that the cost of an average hospital stay
is $9,191 (Ref. 21), FDA finds that $784 million (170,500 x 50 percent
x $9,191) is spent annually on hospitalizations due to potentially
avoidable OTC drug ADR's.
The realized benefits of the rule will depend on the degree to
which consumers are better able to read and understand OTC drug product
labeling and to act on that information to make choices that would
reduce drug side effects, drug interactions, allergic reactions, and
other unintended consequences of self-medicating. If the improved
labeling format and larger print size contributed to the avoidance of
only 5 percent of these hospitalizations, the economic savings would
amount to $39 million annually.
The indirect benefits from reduced drug-related illnesses include
avoided costs due to lost work time or reduced productivity. Roughly 58
percent of adverse drug reaction admissions were for patients aged 20
to 59. The remaining 42 percent of admissions were for patients under
20 years (yx = jNxAx(1/x),
where j = 1 to (x-y)
Total Costy = Costy6 + Costy3 +
Costy2
where:
x = life of labeling in years (2, 3, or 6),
y = implementation period in years,
Nx = number of SKU's with labeling life of x years,
and
Ax = amortized annual value of labeling with a life
of x years.
(Ax is equivalent to the annuity value to pay off an
initial investment, i.e., Ax = C x { I / [1 - (1/ (1 +
I)x)]}; where C = the average weighted cost to redesign a
labeling ($1,500); I = the discount rate (7%); and x = the life of a
labeling in years (2, 3, or 6).)
---------------------------------------------------------------------------
FDA found that, with a 2-year implementation period, the cost of
the proposed requirements would be $19.7 million. To reduce the
economic impact on small entities, the agency proposed an additional 1
year extension for OTC drug products with sales of less than $25,000
per year. Based on the Nielsen data, this extension applied to about 40
percent of OTC drug products, but only about 1 percent of OTC drug
retail sales. With this added deferral, FDA estimated the cost of the
proposed rule at $14.2 million.
3. Response to Comments
A number of comments from the OTC drug industry asserted that the
agency understated the cost of the proposed rule. These comments stated
that: (1) FDA's estimated average cost to redesign labeling was too
low, (2) FDA's methodology to calculate the economic impact of the
proposal was inappropriate, and (3) FDA incorrectly assumed that
package and label sizes would not need to be increased. The following
section addresses each of these issues while focusing primarily on the
comments and alternative economic analysis submitted by NDMA. Appendix
G of NDMA's comment provides a full description of its explanatory data
and methodology (Ref. 25).
NDMA stated that the cost to comply with the proposed rule,
assuming a 2-year implementation period, would be a minimum of $140
million, even without changes to package and label sizes. NDMA
subsequently recommended the use of a net present value approach, which
reduced its cost estimate to $114 million. Further, FDA had proposed an
additional implementation year for SKU's with annual sales below
$25,000. This adjustment reduces NDMA's cost estimate (assuming no
package or label size changes) to $86 million, substantially less than
the originally stated $140 million figure, but still far above FDA's
estimate of $14.2 million.
a. Cost of redesigning drug label. NDMA agreed that FDA
``approached the very complex task of assessing the economic costs
resulting from the proposed rule in a rational, data-based manner'' and
that ``many of the parameters that FDA used as a basis to determine
label design costs were supported by reliable market research data.''
For example, NDMA accepted FDA estimates for both the number and life
cycle of the affected drug labels. Nevertheless, NDMA asserted that the
agency had understated the cost of redesigning a label for the
following reasons: (1) FDA's unit cost estimate was based on a small,
nonrandom sample; (2) FDA was incorrect in eliminating PDP redesign
from the cost of relabeling branded OTC drug products; and (3) FDA did
not consider either the cost of scrapping label inventory or the
administrative burden that would be incurred by firms in developing
compliance strategies.
i. Unit cost estimate (without scrap). NDMA reports that it
developed a cost estimate by surveying 74 member firms regarding the
average cost of redesigning an OTC drug product label. The survey (Ref.
25) requested information on minor and major label changes. Thirty-four
firms responded, of which 31 were brand label manufacturers and 3 were
private label manufacturers. The reported cost per SKU to redesign a
label ranged from $500 to $420,000. Excluding three extreme outliers,
[[Page 13280]]
NDMA projected an average cost (omitting scrap) of $15,154 per SKU to
redesign a branded label and $1,261 for a private label. Assuming a 20/
80 market split for branded and private label products, NDMA calculated
a weighted average cost per SKU of $4,039, roughly double the earlier
FDA estimate (without a PDP adjustment) of $2,070.
To validate its estimate, NDMA cited a cost model that had been
developed by the Research Triangle Institute (RTI) to estimate the
regulatory impact of the NLEA. The RTI model assumed that the cost of
changing a food product label was a function of administrative,
analytical, marketing, printing, and label inventory costs. Printing
costs depended on the type of printing process, the frequency of
redesign, the number of SKU's affected, the complexity of the label
changes, and the length of the compliance period (Ref. 26). NDMA
estimated, based on responses from 21 member firms, that about 50
percent of the industry's SKU's are printed using lithography, 47
percent by flexography, 1 percent by gravure, and the remaining by
other methods. Applying these proportions to the RTI model for complex
printing tasks with four or more color changes, NDMA derived a label
printing cost of $3,458 per SKU for an average OTC drug product and
concluded that this result verified its estimate of $4,039 per SKU
(without scrap).
The agency agrees that the cost data used in FDA's economic
analysis of the proposed rule were not drawn from a random sample,
although they were supplied by sources familiar with the OTC drug
industry, including smaller and private label manufacturers. FDA notes,
however, that the survey underlying the NDMA cost estimates was
likewise not based on a random sample of manufacturers. While NDMA
member firms include a range of large, small, brand-label, and private-
label manufacturers, many smaller firms do not belong to NDMA. Indeed,
NDMA indicates that its 74 members (which may represent less than 20
percent of all OTC drug manufacturers), account for 90 to 95 percent of
all OTC drug sales. A survey limited to this membership necessarily
over-represents large manufacturers of nationally branded products and
under-represents smaller manufacturers of regionally branded products.
Following review of the survey data provided by NDMA, FDA concludes
that NDMA's figures overstate the industry average cost of redesigning
OTC drug labels. For example, the survey reports unreasonably large
differentials between branded and private label manufacturers, with
survey costs for branded SKU's from 3 to 40 times greater than those
for private label SKU's. For graphics development (directions for
studio, draft/mock-ups, review, and concurrence), the average SKU cost
reported was $6,215 for branded and $291 for private label products.
Assuming an hourly wage rate of $40 for branded and private product
personnel, manufacturers of branded products spend 155 hours per SKU on
this function compared to 7 hours by private labelers. For separations
(color mock-ups created and reviewed), the survey reported the per SKU
cost for branded and private label companies at $3,210 and $82,
respectively, almost a 40-fold difference. The agency acknowledges that
large manufactures of nationally branded products involve more
personnel in decision making and may use higher quality packaging
materials. Nevertheless, in view of the substantial degree of market
competition in this industry, private labelers typically package goods
to resemble the competing national brand. Moreover, while questioning
the size of the reported range, FDA could not review the basis for
NDMA's estimates, because the supporting data, such as the number of
labor hours or labor costs used in its calculations, were not
submitted.
Furthermore, while the proposed rule required manufacturers to
reformat the information panels, the NDMA survey instructed respondents
to include the cost of changing all labeling, including certain
promotional materials. Thus, some manufacturers may have reported costs
for developing new product identities, advertising campaigns, etc.
Also, survey respondents were asked to estimate the cost to redesign
only one SKU, which ignores both learning curve and economy of scale
effects. For the most part, the same industry personnel are responsible
for copy and layout decisions for numerous product lines and SKU's.
Moreover, FDA does not agree that the RTI model necessarily validates
NDMA's redesign cost estimate. The portion of the RTI model used by
NDMA was developed to estimate the cost of printing food labels, which
are often considerably larger than OTC drug labels.
NDMA's recent estimate also differs from the average cost of $7,900
per SKU submitted by the Cosmetic, Toiletry, and Fragrance Association
to change a drug-cosmetic label (Ref. 27). OTC drug-cosmetics are
generally considered to have more expensive labeling than OTC drugs
alone, because they compete with other elaborately packaged cosmetic
products.
To finalize its estimate of the average cost of redesigning an OTC
drug label, FDA considered several approaches. First, the agency
maintained its initial estimating methodology, but adjusted the
estimated unit cost per SKU. Based on all available information, FDA
concludes that the cost of redesigning nationally branded products
manufactured by large companies ranges from $5,000 to $15,000 per SKU.
The cost to redesign regional or low sales volume brands of smaller
manufacturers is considerably less, ranging from about $1,000 to $8,000
per SKU. The cost to redesign labels for private label brands is
smaller still, but approximates FDA's original estimate of $1,000 and
NDMA's survey estimate of $1,261 per SKU. Accordingly, to calculate a
final estimate, the agency divided OTC drug products into three
classes: (1) Branded products manufactured by large NDMA member
companies, with a midpoint cost estimate of $10,000 per SKU; (2)
branded products manufactured by smaller companies, with a mid-point
cost estimate of $4,500 per SKU; and (3) private label products,
assumed to cost $1,261 per SKU, as reported by NDMA.
The agency used its original estimate of the SKU distribution,
which indicated that about 30 percent of all OTC drug SKU's are
branded, and the NDMA member survey to determine costing weights to
apply to each industry sector. Respondents to NDMA's survey reported
that they account for about 4,000 branded SKU's, which amount to 15
percent of all branded SKU's. As these survey respondents comprise
almost half of NDMA's membership, FDA assumed that branded products of
all NDMA members may account for about 30 percent of all branded SKU's,
or approximately 10 percent of all affected SKU's (30 percent branded x
30 percent NDMA members). The remaining branded products, therefore,
account for 20 percent of all affected SKU's, and the private label
products account for the remaining 70 percent. This calculation results
in a weighted average cost of $2,783 (without scrap) to redesign a
label (i.e., ($10,000 x 10 percent)+($4,500 x 20 percent)+($1,261 x 70
percent)), a figure higher than the prior FDA estimates but below the
NDMA survey estimate of $4,039.
A second approach was developed by the Eastern Research Group, Inc.
(ERG), a private economics consulting firm under contract to FDA. ERG
developed its model based on data collected during site visits to
several large and small drug
[[Page 13281]]
companies and through discussions with other industry consultants (Ref.
28). ERG assumed a more complex distribution of various types of SKU's
among firms of different sizes and included specific cost variables for
regulatory affairs, art/graphics, manufacturing changes, and inventory
losses by firm size (by employment), firm type (branded or private
label), and type of label changed (carton, container, etc.). Under
ERG's model, the estimated weighted average cost of label redesign
(without scrap) is $1,210 per SKU (Ref. 28).
Because the OTC industry is so diverse and the relevant cost data
are so limited, no single model or single estimate can be viewed as
definitive. Nevertheless, the agency continues to believe that its
overall approach represents a rational basis for estimating the
redesign costs associated with this rule. The agency in its proposed
analysis arrived at an estimate of $2,070 per SKU (without a PDP
adjustment). That figure, when revised to take into account certain
data from the NDMA survey, is increased to $2,783 per SKU. ERG employed
a more complex model and arrived at a figure of $1,210 (or half that of
FDA), while NDMA arrived at a weighted average of $4,039 (or twice that
of FDA). Given this spread, and given the agency's concerns about
NDMA's methodology and input data, the agency is adopting the revised
figure of $2,783 as its base average cost estimate. The agency
acknowledges that it has adopted a conservative figure, relative to
that derived by ERG. However, nothing in the ERG model, or in the NDMA
model, suggests that FDA should discard its methodology or its
assumptions for estimating unit costs.
ii. Principal display panel. In its original analysis, FDA assumed
that the PDP need not be altered and therefore adjusted its unit cost
estimate for branded products downward by 50 percent. NDMA argued that
this correction was inappropriate as it failed to account for many
commonly used labeling and packaging configurations. NDMA pointed out
that, with the exception of labels with separate front and back panels,
all PDP's must be reprinted when the information panel is changed.
Based on a poll of 7-member companies, NDMA estimated that about 90
percent of all OTC drug SKU's require the PDP to be reprinted when
changes are made to the information panel.
The fact that the PDP needs to be reprinted when the information
panel is changed does not mean that it has to be redesigned. For the
majority of labels, the PDP and information labeling are printed as a
single label, with one printing plate required for each of the colors
used. For many products, only one or two colors will be changed on the
information panel to accommodate the new requirements; consequently,
only those plates would need to be redesigned, the others could be
reused or simply copied at significantly reduced cost. Nevertheless,
the agency acknowledges that many manufacturers would, at the time of
redesigning the information panel, also make incremental changes to the
PDP. Therefore, the agency has adopted the NDMA position and eliminated
any downward PDP adjustment from its calculation of the cost of the
final rule.
iii. Scrap. NDMA also argued that the cost of scrapping unused
inventory should be included as a regulatory cost. Based on its survey,
it estimated that scrap labeling inventory adds about $1,000 to the
weighted redesign cost per SKU ($2,968 per SKU for higher cost firms
and $576 per SKU for lower cost firms), raising its average unit cost
estimate to about $5,000. NDMA declared this a conservative estimate
that would underestimate the cost of scrap label inventory if the
implementation date were less than 2 years.
FDA agrees that some scrap label inventory loss is inevitable when
label changes are made, but notes that the longer the implementation
period the easier it is for manufacturers to minimize the cost. The
final rule allows either a 2- or 3-year implementation phase (depending
on sales volume), which is sufficient time to minimize inventory
losses. Because the NDMA survey question failed to state the length of
the phase-in period, the survey response cannot be considered reliable.
Nonetheless, because a better estimate of the average scrap cost is not
available, FDA accepts NDMA's figures, but adjusts the weighting to 10
percent for the higher cost firms and 90 percent for the lower cost
firms, for a weighted average of $800. This weighting is based on the
assumption that both small brand name manufacturers and private label
manufacturers have less expensive labels and smaller inventories than
large brand-name companies. The consideration of scrap, therefore,
raises FDA's weighted average design cost estimate to approximately
$3,600 per SKU.
iv. Administrative costs. NDMA suggested that the agency also
include administrative costs in its calculation of the cost to redesign
the label. NDMA provided no estimate of these costs, but noted that
there would be a burden to manufacturers to manage the additional
required redesign of labels.
FDA agrees that the rule will impose administrative costs, but
concludes that these costs are adequately accounted for in the previous
estimates. OTC drugs are highly regulated products and manufacturers
are expected to have regulatory personnel on staff or consultants
available to address compliance matters. The complexity of the rule is
not unusual compared to other OTC drug regulations and the requirements
will be clear to graphics design and regulatory personnel. Moreover,
the rule is expected to receive widespread publicity when issued and
most OTC drug firms belong to trade associations or have access to
trade publications that provide additional sources of information.
Because the rule permits a 2- to 3-year implementation period, FDA
continues to believe that managing the label changes will not impose
burdens beyond the costs included in the agency's estimate.
b. Methodology for calculating economic impact. NDMA disagreed with
the methodology the agency used to calculate the economic impact of the
proposed rule for two reasons: (1) FDA treated the cost to redesign as
a financed rather than an expensed cost and calculated the impact using
an amortized cost rather than a net present value, and (2) FDA treated
label redesign as an accelerated change rather than an additional
change.
i. Economic versus accounting costs. NDMA asserted that FDA used an
incorrect valuation method to assess the economic impact of the rule,
because the agency's valuation of amortized lost label life incorrectly
implies that the costs of label redesign are financed costs, rather
than sunk costs expensed in the year they incur. According to NDMA, the
proper approach is not to amortize, but to calculate the net present
value of the incremental costs of label redesign.
FDA does not agree that the amortization of lost label life is
inappropriate. Executive Order 12866 charges Federal agencies to
determine the economic cost of its rules, but such costs are not
necessarily identical to financial costs, as interpreted by accounting
convention. According to the U.S. Office of Management and Budget (Ref.
29), the preferred measure for economic analyses is ``the opportunity
cost' of the resources used or the benefits forgone as a result of the
regulatory action.'' Whether firms expense label design costs in the
year they occur is largely irrelevant to the proper calculation of
economic costs, i.e., the opportunity cost of the rule.
[[Page 13282]]
Moreover, FDA's calculation yields results that are identical to those
obtained through a net present value approach. To derive its results,
FDA estimated a net present value and then, for ease of exposition,
converted this figure into an equivalent stream of annual costs.
ii. Additive versus accelerated costs. The primary reason that
NDMA's methodology produces substantially higher costs than FDA's
estimate is that NDMA's approach assumes a ``market driven'' label
cycle that is independent of the design changes required by the rule.
For example, if the average lifetime of a particular label type is 3
years and a design change costs $3,000 per SKU, both FDA and NDMA agree
that a 2-year phase-in would allow two-thirds of the labels to be
replaced under normal business conditions without additional costs
(assuming no package size changes). FDA's methodology, however, also
assumed that the remaining one-third of the labels lose only 1-year of
their expected lifetime, so that the economic cost (ignoring any
discounting adjustment) would be $1,000 per SKU (1/3 x $3,000) for one-
third of these SKU's. This approach, however, implicitly assumes that
the label design cycle would resume at a 3-year interval, so that the
next voluntary label redesign, on average, would not occur until 3
years after the mandated change.
In contrast, NDMA argues that voluntary label redesign occurs in
response to external ``market driven'' factors that would be
independent of this mandated change. According to NDMA, such redesigns
are to change product attribute copy; change graphics; add litigation-
driven warnings; delete ``new'' flags after 6 months; add multilingual
labeling; change labeling information, such as manufacturer,
distributor, or inactive ingredient; or add or change SKU's in a
product line. NDMA contends that, because the mandated changes required
by this rule would not affect the underlying ``market driven'' design
cycle, the full cost of the redesign, rather than just the value of the
remaining life of the former label, measures the economic cost of the
regulation.
With respect to the previous numerical example, NDMA's methodology
implies that those labels that were redesigned in year 2 for regulatory
reasons would, on average, be redesigned again in year 3 for ``market
driven'' reasons. (FDA would assume that the labels that had to be
redesigned in year 2 would not, on average, be redesigned again until
year 5.) NDMA's methodology, therefore, would calculate the economic
cost at about $3,000 per affected SKU, compared to FDA's estimate of
about $1,000.
The agency does not dispute the theoretical possibility of NDMA's
argument. If ``market driven'' reasons for label adjustments always
compelled an immediate response, companies could not coordinate
voluntary label updates with mandatory label redesign; the regulatory
cost for each affected label, therefore, would be the full cost of the
design change. However, FDA does not agree that such abrupt shifts in
marketing strategies are the industry norm. Many of the examples of
``market driven'' label changes NDMA cited are for exactly the kind of
incremental adjustments that would be deferred and consolidated in a
major redesign effort. For example, the demand for most changes to
product attribute copy or graphics mounts gradually in response to
shifting advertising and marketing styles. Once changed, such
modifications postpone the need for future change. Revisions for
litigation-driven warnings are less common events that would be
expected to have a small effect on industry averages. According to the
RTI study (Ref. 26), line copy changes or changes affecting just one
color are minor changes that, in most cases, are made without the
assistance of a label artist and cost one-sixth the cost of a four-or-
more color change. Such minor adjustments would not be expected to
alter the underlying design cycle.
The agency finds it more likely that the demand for most major
label changes is a steadily increasing function of the time that has
elapsed since the last labeling revision and that manufacturers
continually refine marketing techniques and strategies. As most
companies will find it cost-effective to complete these incremental
labeling changes concurrently with the mandatory redesign required by
this rule, FDA's revised analysis maintains the assumption that the
current labeling change cycle will continue unaltered. Moreover, it is
important to note that the agency's decision not to exclude PDP design
costs is based on its finding that incremental style modifications
accompany mandated changes. If firms would not bundle incremental style
changes with the mandated changes, the PDP design costs should be
subtracted from the regulatory cost estimate.
c. Cost of increasing size of packages and/or labels. Several
comments objected to FDA's assumption that the proposed rule would
require few changes to the size or configuration of OTC drug packages
or labels. NDMA reported that its survey indicated that 33 percent of
branded and 95 percent of private label SKU's could not accommodate the
proposed label format. NDMA estimated that exemption petitions would be
filed for 33,500 SKU's, that 32,600 SKU's would alter package
configuration at a cost of over $1 billion, and that about 15,500 SKU's
would be removed from the market. While not including administrative
costs for feasibility studies to determine cost-effective packaging and
labeling configurations, NDMA stated that they would be large. One
manufacturer suggested that a new packaging line to accommodate a label
change for just one product line would result in a one-time equipment
expenditure of about $2.5 million (including equipment, installation,
validation, depreciation of old equipment, facility renovation, and
inventory loss) and recurring costs of almost $500,000 for the more
expensive labeling.
The previously mentioned projections greatly overestimate the
percentage of SKU's that will not be able to accommodate the new format
and the cost of increasing the size of the labeling, where necessary.
In particular, the assertion that 95 percent of private label SKU's
could not accommodate the proposal requirements is difficult to
understand, as the vast majority of private label OTC drug products are
packaged almost identically to the leading branded products for
competitive reasons. Moreover, the agency carefully reviewed labels
submitted as examples of those that would not fit the proposed format
and found that many could, in fact, accommodate the final rule without
a change in label or package size.
FDA also questions the methodology for calculating the costs of
package size changes. Although details of these calculations were not
submitted, it appears that NDMA estimated the cost of purchasing or
modifying equipment by multiplying the unit costs by the number of
affected SKU's, with no allowance for multiple SKU's packaged on a
given production line, or for the widespread usage of contract
packagers. Although agreeing that such factors should be considered
when determining costs, NDMA nonetheless assumed substantial equipment
requirements for each SKU. Moreover, NDMA does not differentiate
between the costs of branded and private label manufacturers. Most
private label products are manufactured by firms that produce hundreds
of SKU's on the same equipment, as most packaging machines can
accommodate a spectrum of changes with only minor modification or
retooling. As firms will choose the most cost-effective means of
implementing
[[Page 13283]]
package changes, only in rare cases, or when equipment is already
obsolete, should the rule lead to the purchase of new equipment.
For some small SKU's, the impact of this rule will be moderated by
the more flexible leading and formatting provisions in the final rule
and the modified small package format allowed in 201.66(d)(10). FDA
further believes that any reduced consumer choice, should a small
package product not be able to meet the new requirements, will be
relatively insignificant because most manufacturers offer products in
more than one package size.
To respond fully to the estimates offered by NDMA, FDA asked its
economics consultant, ERG, to survey (Ref. 28) all of the OTC drug
products found on the shelves in three retail outlets in the Boston
area. These outlets included: (1) A large pharmacy chain, (2) an
independent pharmacy, and (3) a convenience store. ERG examined each of
the 2,689 distinct SKU's found on the store shelves, and recorded data
on the package size and type, the available labeling space, and the
font size. ERG then compared these data to generic mock-ups of the
revised monographs to estimate the percent of the SKU's that might need
to increase the size of either the label or package. ERG also estimated
the amount of the additional space needed to accommodate the new format
for those SKU's that lacked sufficient labeling surface area, using an
expansion factor to derive estimates for SKU's for which no adequate
mock-ups were available.
The results of the survey are shown by type of package in Table 4
of this document. The vast majority of SKU's, 92 percent, have
sufficient labeling space to accommodate the revised format. Of these,
16 percent will require some reconfiguration of the current information
presentation, such as moving, reducing, or eliminating certain
marketing information. Another 1.7 percent of the SKU's would increase
the size of their label to accommodate the new format and 6.4 percent
either would not fit or were indeterminate (too close to call) and,
thus, might require a new packaging configuration. (SKU's were judged
indeterminate when the available labeling area was within 5 square
centimeters of the required area.)
Table 4.--Findings for 6.0-Point Font, Condensed Type Allowed1
------------------------------------------------------------------------
Percent of
Labeling outcome SKU's
------------------------------------------------------------------------
Revised label can fit using existing area allotted for 75.9
regulatory information
Revised label fits if area allotted for regulatory 16.0
information is increased
Revised label fits if expanded on existing container 1.7
Revised label will not fit 4.5
Indeterminate 1.9
Total 100
------------------------------------------------------------------------
\1\ Horizontal width of the characters reduced by approximately 20
percent while the vertical height of the characters is unchanged.
To evaluate the estimate of reconfiguration costs (i.e., changes to
the size of the labeling or packaging) presented in the comments, ERG
considered several options for packaging changes, including adding a
carton (if not already present), adding a fifth panel, increasing the
size of the packaging, or switching to a nonstandard form of labeling
such as peel-back or accordion labels (Ref. 28). Where applicable, the
costs for changing a container size included container inventory loss,
adjustment of the packaging line, and stability testing. The estimated
packaging change costs varied with the option chosen (for example,
adjustment or retooling of existing machinery versus the purchase of
new equipment), although the lower cost options had a higher
probability of selection. ERG also considered the recurring annual
costs that would be associated with the need for larger labels or
packages. A detailed description of ERG's assumptions, calculations,
and unit costs is presented in the full report.
4. Total Incremental Costs
The costs of labeling redesign apply only to products covered by
final OTC drug monographs or applications. Currently there are about
39,310 SKU's in this category (see Table 3 of this document). No
redesign costs are assigned to the remaining 59,330 SKU's because the
6-year implementation period for these products will allow
manufacturers to incorporate the design changes in their usual redesign
cycle. Using a weighted average cost to redesign a label of $3,600 per
SKU and assuming labels are redesigned voluntarily every 2, 3, or 6
years, the total incremental costs for redesigning labeling using the
methodology discussed earlier is $19.4 million.
Reconfiguration costs apply to those products that cannot
accommodate the small package format allowed in Sec. 201.66(d)(10).
These costs include the one-time cost to increase labeling size (the
label or package, where applicable) to accommodate a minimum 6.0
condensed font, plus the recurring cost of producing larger labeling.
Because these costs are applied to this rule regardless of the
monograph status of the product, all 98,639 SKU's are potentially
subject to label reconfiguration costs; 39,310 within 2 years of the
effective date of this final rule, the remaining 59,330 within 6 years
of the effective date of this final rule. The estimated reconfiguration
costs amount to $38.1 million in one-time costs and $11.5 million in
annual recurring costs. The latter reflects the incremental increases
in labeling or packaging materials to accommodate the format
requirements.
Table 5 of this document presents FDA's estimate of the one-time
and annual recurring costs and the total annualized cost by compliance
activity. The total one-time costs of $57.5 million include $19.4
million for label redesign and $38.1 million for packaging changes. The
annual costs are $11.5 million. The total annualized cost to industry
(using a 7 percent discount rate) is estimated at $18.4 million. The
cost to individual firms will vary with the number of SKU's, the type
of changes needed, and the timing of the changes.
[[Page 13284]]
Table 5.--Total Industry Compliance Costs
------------------------------------------------------------------------
One-Time Annual Total
Activity ($Million) ($Million) Annualized
------------------------------------------------------------------------
Label redesign 19.4 NA 1.4
Packaging 38.1 11.5 17.0
Total 57.5 11.5 18.4
------------------------------------------------------------------------
These estimates may overstate the costs attributable to this rule.
First, reconfiguration costs will be reduced to the extent that
companies opt to eliminate some smaller packaging sizes within a
product line. In these instances, however, consumers will bear some of
the added costs. Second, the recent amendment to section 502(e) of the
act under FDAMA requires that OTC drug manufacturers list the inactive
ingredients in their labeling. The ERG retail outlet survey (Ref. 28)
found that about 7 percent of the SKU's currently do not include
inactive ingredients on their labels. Some of these products may need
larger label or package sizes irrespective of this rule.
D. Small Business Impact
Manufacturers and those entities that engage in the relabeling of
OTC drug products will be required to redesign the labeling of their
products to comply with this rule. Census data provide aggregate
industry statistics on the number of manufacturers for Standardized
Industrial Classification Code 2834, Pharmaceutical Preparations, by
establishment size, but do not distinguish between manufacturers of
prescription and OTC drugs. Over 92 percent of the roughly 700
establishments and over 87 percent of the 650 firms in this sector have
fewer than 500 employees. The Small Business Administration (SBA)
considers firms with fewer than 750 employees in this industry to be
small, but the U.S. Census size categories do not correspond to the SBA
designation. An alternative data source, IMS, identified roughly 400
firms as manufacturers of OTC drug products. Using the SBA size
designation of 750 employees, about 70 percent of the 400 affected
manufacturing firms would be considered small.
This regulation will affect the information content and format
associated with OTC drug product labeling. Firms that manufacture or
relabel OTC drug products will need to change the information panel for
each affected product and may need to increase the size of the
packaging or labeling for a few SKU's. These costs will be mitigated,
however, by the several year implementation period, which will permit
many of these changes to be coordinated with those labeling changes
conducted in the normal course of business. OTC drug products subject
to new drug and ANDA's will need to submit revised labeling to the
agency in accordance with Sec. 314.70. This is a standard procedure
that companies routinely follow for labeling changes. The final rule
will not require new reporting and recordkeeping activities. Therefore,
no additional professional skills are necessary.
The economic impact of this rule on small firms is particularly
difficult to measure, because published financial data do not
distinguish between firms manufacturing mostly OTC drugs and firms
manufacturing mostly prescription drugs. ERG adopted Census data on
firm size and revenue for SIC 2834, Pharmaceutical Preparations, and
assumed 400 manufacturers of OTC drug products to derive the figures in
Table 6 of this document. These data indicate that if 90 percent of the
OTC drug product firms meet the SBA size criteria for small businesses,
the annualized industry cost attributed to small businesses would
amount to $12.3 million out of the total $18.4 million. If revenues of
small OTC drug product manufacturers are similar to those of all small
manufacturers in SIC 2834, these costs represent only 0.17 percent of
small business OTC drug revenues.
Table 6.--Small Business Impact
----------------------------------------------------------------------------------------------------------------
OTC Manufacturing Total OTC Small Business Total
----------------------------------------------------------------------------------------------------------------
Firms 400 357
Establishments 478 374
Employees 86,849 18,942
Average employees per firm 217 53
Percentage of total small business employment NA 100%
Receipts ($000) $42,363,000 $7,411,000
Receipts per firm ($000) $106,000 $21,000
Total SKU's affected 98,639 65,792
As percentage of all SKU's 100% 66.7%
Total annualized compliance costs ($ millions) $18.4 $12.3
Total annualized compliance costs as percentage of 0.0004 0.0017
annual revenues
----------------------------------------------------------------------------------------------------------------
These calculations, however, assume that small businesses can
finance the one-time outlays over time. In fact, some small firms may
have difficulty raising the funds. FDA finds that, on average, the
incremental one-time cost per SKU is about $600 ($57.5 million
98,639 SKU's). If a small firm manufactures 10 or 20 SKU's, it might
need to raise from $6,000 to $12,000 within the permitted
implementation period. In view of the figures developed for Table 6 of
this document, which imply that the annual revenue per SKU averages
about $100,000 for small businesses, such one-time outlays should be
manageable for most small firms.
The agency has taken a number of steps to minimize the impact on
small entities, including: (1) A 2- to 6- year implementation period to
allow the sale of existing product inventories and to permit
coordination of required labeling changes with routine industry-
initiated labeling changes, (2) a modified format for small packages,
(3) an additional phase-in year for OTC drug products covered by a
final monograph or an
[[Page 13285]]
approved drug application if yearly sales are less than $25,000, and
(4) coordination of the FDAMA requirement for listing inactive
ingredients with the implementation of this rule. These provisions will
provide additional flexibility and cost savings for small entities.
E. Alternatives
The major regulatory alternatives considered included various
implementation periods and graphics features, including font sizes and
print types. As shown in Table 7 of this document, redesign costs for
the 39,310 SKU's with a final monograph decrease substantially with
longer implementation periods for products covered by final monographs
or approved drug applications. One-time costs for a 1-year
implementation period would be about $59.1 million. A 2-year
implementation period reduces this figure to $27 million and a 3-year
period to $11.9 million. The selected alternative, which includes the
2-year implementation period, but permits a third year for products
with low volume sales, reduces these redesign costs to $19.4 million.
The agency believes this implementation period will provide substantial
relief to industry while achieving important consumer safety and use
goals in a timely manner.
Table 7.--Effect of Implementation Period on Redesign Costs
------------------------------------------------------------------------
Redesign Cost With 1
Implementation Additional Year for Low
Period for Final Cost ($ Millions) Volume Products ($
Monographs Millions)
------------------------------------------------------------------------
1 year 59.1 46.9
2 years 27.0 19.4
3 years 11.9 8.9
------------------------------------------------------------------------
FDA also considered alternative requirements for minimum font sizes
and print types. Table 8 of this document presents, for several
alternatives, ERG's estimates of the percent of SKU's with current
labels too small to fit, the one-time costs for labeling
reconfiguration, and the recurring label, carton, and container costs,
under varied font size and print requirements. The annualized cost for
a minimum 6.0 font but not condensed type (i.e., the horizontal width
of the characters reduced approximately 10 to 20 percent while the
vertical height of the characters is unchanged) requirement would be
$25 million. The final rule allows condensed print, which reduces this
cost to $17 million. The agency considered but rejected labeling with
smaller than 6-point type size because of the readability issues
associated with such labeling.
Table 8.--Effect of Print Requirements on Labeling Reconfiguration Costs
--------------------------------------------------------------------------------------------------------------------------------------------------------
Recurring Incremental
Percent of SKU's That One-Time Packaging Label, Carton and Total Annualized
Minimum Font Size, Print Type Required Cannot Fit or Are Reconfiguration ($ Container Materials ($ Packaging Cost ($
Indeterminate Millions) Millions) Millions)
--------------------------------------------------------------------------------------------------------------------------------------------------------
6.0, not condensed 9.5 45.9 18.3 25.0
6.0, condensed allowed 6.4 38.1 11.5 17.0
4.5, not condensed 3.4 21.0 5.1 8.2
4.5, condensed allowed 2.3 14.0 3.4 5.4
--------------------------------------------------------------------------------------------------------------------------------------------------------
This final rule has been determined to be a major rule for purposes
of 5 U.S.C. 801 et. seq., subtitle E of the Small Business Regulatory
Enforcement Fairness Act of 1996 (Pub. L. 104-121). FDA is submitting
the information and reports as required by the statute.
IX. References
The following references are on display in the Dockets Management
Branch (address above) and may be seen by interested persons between 9
a.m. and 4 p.m., Monday through Friday.
1. Miller, G. A., ``The Magical Number Seven, Plus or Minus Two:
Some limits on Our Capacity for Processing Information,''
Psychological Review, 101(2):343-352, 1994.
2. Shiffrin, R. M., and R. M. Nosofsky, ``Seven Plus or Minus
Two: A Commentary On Capacity Limitations,'' Psychological Review,
101(2):357-361, 1994.
3. Allen, P. A., and L. C. Crozier, ``Age and Ideal Chunk
Size,'' Journal of Gerontology: Psychological Sciences, 47(1):47-51,
1992.
4. Wood, R., and A. Bandura, ``Impact of Conceptions of Ability
on Self-Regulatory Mechanisms and Complex Decision Making,'' Journal
of Personality and Social Psychology, 56(3): 407-415, 1989.
5. Chandler, P., and J. Sweller, ``Cognitive Load Theory and the
Format of Instruction,'' Cognition and Instruction, 8(4):293-332,
1991.
6. Food and Drug Administration, ``National Uniformity for
Nonprescription Drugs--Ingredient Listing for OTC Drugs,'' April
1998, Docket No. 98D-0149, Dockets Management Branch.
7. Comment No. 718, Docket No. 96P-0318, Dockets Management
Branch.
8. Comment No. 684, Docket No. 96P-0318, Dockets Management
Branch.
9. Webster's Ninth New Collegiate Dictionary, p. 371, 1990.
10. Nonprescription Drug Manufacturers Association, ``Label
Readability Guidelines,'' May 1996, in OTC vol. 28FR, Docket No.
96N-0420, Dockets Management Branch.
11. Watanabe, R. K., ``The Ability of the Geriatric Population
to Read Labels on Over-the-Counter Medication Containers,'' Journal
of the American Optometric Association, 65:32-37, 1994.
12. Comment No. CP1, Docket No. 96P-0318, Dockets Management
Branch.
13. Letter from R. G. Chesemore, FDA, to B. Nakutin, dated April
22, 1997, coded PDN1, Docket No. 96P-0318, Dockets Management
Branch.
14. Food and Drug Administration ``Consumer Comprehension and
Preference for Variation in the Proposed Over-the-Counter Drug
Labeling Format,'' in OTC vol. 28FR, Docket No. 96N-0420, Dockets
Management Branch.
15. Levy, A. S., S. B. Fein, and R. E. Schucker, ``More
Effective Nutrition Label Formats Are Not Necessarily More
Preferred,'' Journal of the American Dietetic Association,
92(10):1230-1234, 1992.
16. Einarson, T. R., ``Drug-Related Hospital Admissions,'' The
Annals of Pharmacotherapy, 27:832-840, 1993.
17. Ives, T. J., E. J. Bentz, and R. E. Gwyther, ``Drug-Related
Admissions to a Family Medicine Inpatient Service,'' Archives of
Internal Medicine, 147:1117-1120, 1987.
18. Caranasos, G. J., R. Stewart, and L. E. Cluff, ``Drug-
induced Illness Leading to
[[Page 13286]]
Hospitalization,'' Journal of the American Medical Association,
228:713-7171, 1974.
19. Mitchell, A. A. et al., ``Adverse Drug Reactions in Children
Leading to Hospital Admission,'' Pediatrics, 82:24-29, 1988.
20. Classen, D. C. et al., ``Adverse Drug Events in Hospitalized
Patients,'' Journal of the American Medical Association, 277(4):301-
306, 1997.
21. Agency for Health Care Policy and Research, ``National
Medical Expenditure Survey: Annual Expenses and Sources of Payment
for Health Care Services Research Findings 14,'' p. 7, 1995.
22. McKenney, J. M., and W. L. Harrison, ``Drug-related Hospital
Admissions,'' American Journal of Hospital Pharmacists, 33:792-795,
1976.
23. U.S. Department of Commerce, ``Statistical Abstract of the
United States 1998,'' The National Data Book, Table 683, 118:426,
1998.
24. U.S. Department of Commerce, ``1992 Census of Retail Trade;
Establishment and Firm Size,'' Table 3, pp. 56, 57, and 68, 1992.
25. Comment No. 716, Supplement No. 2 (attachment 1, appendix
G), Docket No. 96N-0420, Dockets Management Branch.
26. Research Triangle Institute, ``Compliance Cost of Food
Labeling Regulations: Final Report (January, 1991),'' FDA contract
number 223-87-2097, Docket Nos. 90N-0134 and 90N-0135, Dockets
Management Branch.
27. Comment No. C717, Docket No. 96N-0420, Dockets Management
Branch.
28. Eastern Research Group, Inc., ``Cost Impacts of the Over-
the-Counter Pharmaceutical Labeling Rule,'' in OTC vol. 28FR, Docket
No. 96N-0420, Dockets Management Branch.
29. Office of Management and Budget, ``Economic Analysis of
Federal Regulations Under Executive Order 12866,'' 1996.
List of Subjects
21 CFR Part 201
Drugs, Labeling, Reporting and recordkeeping requirements.
21 CFR Part 330
Over-the-counter drugs.
21 CFR Parts 331, 341, 346, 355, and 358
Labeling, Over-the-counter drugs.
21 CFR Part 369
Labeling, Medical devices, Over-the-counter drugs.
21 CFR Part 701
Cosmetics, Labeling, Reporting and recordkeeping requirements.
Therefore, under the Federal Food, Drug, and Cosmetic Act, the
Public Health Service Act, and under authority delegated to the
Commissioner of Food and Drugs, 21 CFR parts 201, 330, 331, 341, 346,
355, 358, 369, and 701 are amended as follows:
PART 201--LABELING
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.
2. Section 201.63 is amended by revising the section heading, the
first sentence in paragraph (a), and paragraph (e) to read as follows:
Sec. 201.63 Pregnancy/breast-feeding warning.
(a) The labeling for all over-the-counter (OTC) drug products that
are intended for systemic absorption, unless specifically exempted,
shall contain a general warning under the heading ``Warning'' (or
``Warnings'' if it appears with additional warning statements) as
follows: ``If pregnant or breast-feeding, ask a health professional
before use.'' [first four words of this statement in bold type] * * *
* * * * *
(e) The labeling of orally or rectally administered OTC aspirin and
aspirin-containing drug products must bear a warning that immediately
follows the general warning identified in paragraph (a) of this
section. The warning shall be as follows:
``It is especially important not to use'' (select ``aspirin'' or
``carbaspirin calcium,'' as appropriate) ``during the last 3 months of
pregnancy unless definitely directed to do so by a doctor because it
may cause problems in the unborn child or complications during
delivery.''
3. Section 201.64 is amended by revising the last sentence in
paragraph (b) to read as follows:
Sec. 201.64 Sodium labeling.
* * * * *
(b) * * * The sodium content per dosage unit shall follow the
heading ``Other information'' as stated in Sec. 201.66(c)(7).
* * * * *
4. Section 201.66 is added to subpart C to read as follows:
Sec. 201.66 Format and content requirements for over-the-counter (OTC)
drug product labeling.
(a) Scope. This section sets forth the content and format
requirements for the labeling of all OTC drug products. Where an OTC
drug product is the subject of an applicable monograph or regulation
that contains content and format requirements that conflict with this
section, the content and format requirements in this section must be
followed unless otherwise specifically provided in the applicable
monograph or regulation.
(b) Definitions. The following definitions apply to this section:
(1) Act means the Federal Food, Drug, and Cosmetic Act (secs. 201
et seq. (21 U.S.C. 321 et seq.)).
(2) Active ingredient means any component that is intended to
furnish pharmacological activity or other direct effect in the
diagnosis, cure, mitigation, treatment, or prevention of disease, or to
affect the structure or any function of the body of humans. The term
includes those components that may undergo chemical change in the
manufacture of the drug product and be present in the drug product in a
modified form intended to furnish the specified activity or effect.
(3) Approved drug application means a new drug (NDA) or abbreviated
new drug (ANDA) application approved under section 505 of the act (21
U.S.C. 355).
(4) Bullet means a geometric symbol that precedes each statement in
a list of statements. For purposes of this section, the bullet style is
limited to solid squares or solid circles, in the format set forth in
paragraph (d)(4) of this section.
(5) Established name of a drug or ingredient thereof means the
applicable official name designated under section 508 of the act (21
U.S.C. 358), or, if there is no designated official name and the drug
or ingredient is recognized in an official compendium, the official
title of the drug or ingredient in such compendium, or, if there is no
designated official name and the drug or ingredient is not recognized
in an official compendium, the common or usual name of the drug or
ingredient.
(6) FDA means the Food and Drug Administration.
(7) Heading means the required statements in quotation marks listed
in paragraphs (c)(2) through (c)(9) of this section, excluding
subheadings (as defined in paragraph (a)(9) of this section).
(8) Inactive ingredient means any component other than an active
ingredient.
(9) Subheading means the required statements in quotation marks
listed in paragraphs (c)(5)(ii) through (c)(5)(vii) of this section.
(10) Drug facts labeling means the title, headings, subheadings,
and information required under or otherwise described in paragraph (c)
of this section.
(11) Title means the heading listed at the top of the required OTC
drug product labeling, as set forth in paragraph (c)(1) of this
section.
[[Page 13287]]
(12) Total surface area available to bear labeling means all
surfaces of the outside container of the retail package or, if there is
no such outside container, all surfaces of the immediate container or
container wrapper except for the flanges at the tops and bottoms of
cans and the shoulders and necks of bottles and jars.
(c) Content requirements. The outside container or wrapper of the
retail package, or the immediate container label if there is no outside
container or wrapper, shall contain the title, headings, subheadings,
and information set forth in paragraphs (c)(1) through (c)(8) of this
section, and may contain the information under the heading in paragraph
(c)(9) of this section, in the order listed.
(1) (Title) ``Drug Facts''. If the drug facts labeling appears on
more than one panel, the title ``Drug Facts (continued)'' shall appear
at the top of each subsequent panel containing such information.
(2) ``Active ingredient'' or ``Active ingredients'' ``(in each
[insert the dosage unit stated in the directions for use (e.g., tablet,
5 mL teaspoonful) or in each gram as stated in Secs. 333.110 and
333.120 of this chapter])'', followed by the established name of each
active ingredient and the quantity of each active ingredient per dosage
unit. Unless otherwise provided in an applicable OTC drug monograph or
approved drug application, products marketed without discrete dosage
units (e.g., topicals) shall state the proportion (rather than the
quantity) of each active ingredient.
(3) ``Purpose'' or ``Purposes'', followed by the general
pharmacological category(ies) or the principal intended action(s) of
the drug or, where the drug consists of more than one ingredient, the
general pharmacological categories or the principal intended actions of
each active ingredient. When an OTC drug monograph contains a statement
of identity, the pharmacological action described in the statement of
identity shall also be stated as the purpose of the active ingredient.
(4) ``Use'' or ``Uses'', followed by the indication(s) for the
specific drug product.
(5) ``Warning'' or ``Warnings'', followed by one or more of the
following, if applicable:
(i) ``For external use only'' [in bold type] for topical drug
products not intended for ingestion, or ``For'' (select one of the
following, as appropriate: ``rectal'' or ``vaginal'') ``use only'' [in
bold type].
(ii) All applicable warnings listed in paragraphs (c)(5)(ii)(A)
through (c)(5)(ii)(G) of this section with the appropriate subheadings
highlighted in bold type:
(A) Allergic reaction warnings set forth in any applicable OTC drug
monograph or approved drug application for any product that requires a
separate allergy warning. This warning shall follow the subheading
``Allergy alert:''
(B) Reye's syndrome warning for drug products containing
salicylates set forth in Sec. 201.314(h)(1). This warning shall follow
the subheading ``Reye's syndrome:''
(C) Flammability warning, with appropriate flammability signal word
(e.g., Secs. 358.150(c) and 358.550(c) of this chapter). This warning
shall follow a subheading containing the appropriate flammability
signal word described in an applicable OTC drug monograph or approved
drug application.
(D) Water soluble gums warning set forth in Sec. 201.319. This
warning shall follow the subheading ``Choking:''
(E) Alcohol warning set forth in Sec. 201.322. This warning shall
follow the subheading ``Alcohol warning:''
(F) Sore throat warning set forth in Sec. 201.315. This warning
shall follow the subheading ``Sore throat warning:''
(G) Warning for drug products containing sodium phosphates set
forth in Sec. 201.307(b)(2)(i) or (b)(2)(ii). This warning shall follow
the subheading ``Dosage warning:''
(iii) ``Do not use'' [in bold type], followed by all
contraindications for use with the product. These contraindications are
absolute and are intended for situations in which consumers should not
use the product unless a prior diagnosis has been established by a
doctor or for situations in which certain consumers should not use the
product under any circumstances regardless of whether a doctor or
health professional is consulted.
(iv) ``Ask a doctor before use if you have'' [in bold type] or, for
products labeled only for use in children under 12 years of age, ``Ask
a doctor before use if the child has'' [in bold type], followed by all
warnings for persons with certain preexisting conditions (excluding
pregnancy) and all warnings for persons experiencing certain symptoms.
The warnings under this heading are those intended only for situations
in which consumers should not use the product until a doctor is
consulted.
(v) ``Ask a doctor or pharmacist before use if you are'' [in bold
type] or, for products labeled only for use in children under 12 years
of age, ``Ask a doctor or pharmacist before use if the child is'' [in
bold type], followed by all drug-drug and drug-food interaction
warnings.
(vi) ``When using this product'' [in bold type], followed by the
side effects that the consumer may experience, and the substances
(e.g., alcohol) or activities (e.g., operating machinery, driving a
car, warnings set forth in Sec. 369.21 of this chapter for drugs in
dispensers pressurized by gaseous propellants) to avoid while using the
product.
(vii) ``Stop use and ask a doctor if'' [in bold type], followed by
any signs of toxicity or other reactions that would necessitate
immediately discontinuing use of the product.
(viii) Any required warnings in an applicable OTC drug monograph,
other OTC drug regulations, or approved drug application that do not
fit within one of the categories listed in paragraphs (c)(5)(i) through
(c)(5)(vii), (c)(5)(ix), and (c)(5)(x) of this section.
(ix) The pregnancy/breast-feeding warning set forth in
Sec. 201.63(a); the third trimester warning set forth in Sec. 201.63(e)
for products containing aspirin or carbaspirin calcium; the third
trimester warning set forth in approved drug applications for products
containing ketoprofen, naproxen sodium, and ibuprofen (not intended
exclusively for use in children).
(x) The ``Keep out of reach of children'' warning and the
accidental overdose/ingestion warning set forth in Sec. 330.1(g) of
this chapter.
(6) ``Directions'', followed by the directions for use described in
an applicable OTC drug monograph or approved drug application.
(7) ``Other information'', followed by additional information that
is not included under paragraphs (c)(2) through (c)(6), (c)(8), and
(c)(9) of this section, 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.
(i) Required information about certain ingredients in OTC drug
products (e.g., sodium in Sec. 201.64(c)) shall appear as follows:
``each (insert appropriate dosage unit) contains:'' [in bold type]
(insert name(s) of ingredient(s) and the quantity of each ingredient).
This information shall be the first statement under this heading.
(ii) The phenylalanine/aspartame content required by
Sec. 201.21(b), if applicable, shall appear as the next item of
information.
(iii) Additional information that is authorized to appear under
this heading shall appear as the next item(s) of information. There is
no required order for this subsequent information.
[[Page 13288]]
(8) ``Inactive ingredients'', followed by a listing of the
established name of each inactive ingredient. If the product is an OTC
drug product that is not also a cosmetic product, then the inactive
ingredients shall be listed in alphabetical order. If the product is an
OTC drug product that is also a cosmetic product, then the inactive
ingredients shall be listed as set forth in Sec. 701.3(a) or (f) of
this chapter, the names of cosmetic ingredients shall be determined in
accordance with Sec. 701.3(c) of this chapter, and the provisions in
Sec. 701.3(e), (g), (h), (l), (m), (n), and (o) of this chapter and
Sec. 720.8 of this chapter may also apply, as appropriate. If there is
a difference in the labeling provisions in this Sec. 201.66 and
Secs. 701.3 and 720.8 of this chapter, the labeling provisions in this
Sec. 201.66 shall be used.
(9) ``Questions?'' or ``Questions or comments?'', followed by the
telephone number of a source to answer questions about the product. It
is recommended that the days of the week and times of the day when a
person is available to respond to questions also be included. A graphic
of a telephone or telephone receiver may appear before the heading. The
telephone number must appear in a minimum 6-point bold type.
(d) Format requirements. The title, headings, subheadings, and
information set forth in paragraphs (c)(1) through (c)(9) of this
section shall be presented on OTC drug products in accordance with the
following specifications. In the interest of uniformity of
presentation, FDA strongly reccommends that the Drug Facts labeling be
presented using the graphic specifications set forth in appendix A to
part 201.
(1) The title ``Drug Facts'' or ``Drug Facts (continued)'' shall
use uppercase letters for the first letter of the words ``Drug'' and
``Facts.'' All headings and subheadings in paragraphs (c)(2) through
(c)(9) of this section shall use an uppercase letter for the first
letter in the first word and lowercase letters for all other words. The
title, headings, and subheadings in paragraphs (c)(1), (c)(2), and
(c)(4) through (c)(9) of this section shall be left justified.
(2) The letter height or type size for the title ``Drug Facts''
shall appear in a type size larger than the largest type size used in
the Drug Facts labeling. The letter height or type size for the title
``Drug Facts (continued)'' shall be no smaller than 8-point type. The
letter height or type size for the headings in paragraphs (c)(2)
through (c)(9) of this section shall be the larger of either 8-point or
greater type, or 2-point sizes greater than the point size of the text.
The letter height or type size for the subheadings and all other
information described in paragraphs (c)(2) through (c)(9) of this
section shall be no smaller than 6-point type.
(3) The title, headings, subheadings, and information in paragraphs
(c)(1) through (c)(9) of this section shall be legible and clearly
presented, shall not appear in reverse type, shall have at least 0.5-
point leading (i.e., space between two lines of text), and shall not
have letters that touch. The type style for the title, headings,
subheadings, and all other required information described in paragraphs
(c)(2) through (c)(9) of this section shall be any single, clear, easy-
to-read type style, with no more than 39 characters per inch. The title
and headings shall be in bold italic, and the subheadings shall be in
bold type, except that the word ``(continued)'' in the title ``Drug
Facts (continued)'' shall be regular type. The type shall be all black
or one dark color, printed on a white or other light, neutral color,
contrasting background, except that the title and the headings may be
presented in a single, alternative, contrasting dark color unless
otherwise provided in an approved drug application, OTC drug monograph
(e.g., current requirements for bold print in Secs. 341.76 and 341.80
of this chapter), or other OTC drug regulation (e.g., the requirement
for a box and red letters in Sec. 201.308(c)(1)).
(4) When there is more than one statement, each individual
statement listed under the headings and subheadings in paragraphs
(c)(4) through (c)(7) of this section shall be preceded by a solid
square or solid circle bullet of 5-point type size. Bullets shall be
presented in the same shape and color throughout the labeling. The
first bulleted statement on each horizontal line of text shall be
either left justified or separated from an appropriate heading or
subheading by at least two square ``ems'' (i.e., two squares of the
size of the letter ``M''). If more than one bulleted statement is
placed on the same horizontal line, the end of one bulleted statement
shall be separated from the beginning of the next bulleted statement by
at least two square ``ems'' and the complete additional bulleted
statement(s) shall not continue to the next line of text. Additional
bulleted statements appearing on each subsequent horizontal line of
text under a heading or subheading shall be vertically aligned with the
bulleted statements appearing on the previous line.
(5) The title, headings, subheadings, and information set forth in
paragraphs (c)(1) through (c)(9) of this section may appear on more
than one panel on the outside container of the retail package, or the
immediate container label if there is no outside container or wrapper.
The continuation of the required content and format onto multiple
panels must retain the required order and flow of headings,
subheadings, and information. A visual graphic (e.g., an arrow) shall
be used to signal the continuation of the Drug Facts labeling to the
next adjacent panel.
(6) The heading and information required under paragraph (c)(2) of
this section shall appear immediately adjacent and to the left of the
heading and information required under paragraph (c)(3) of this
section. The active ingredients and purposes shall be aligned under the
appropriate headings such that the heading and information required
under paragraph (c)(2) of this section shall be left justified and the
heading and information required under paragraph (c)(3) of this section
shall be right justified. If the OTC drug product contains more than
one active ingredient, the active ingredients shall be listed in
alphabetical order. If more than one active ingredient has the same
purpose, the purpose need not be repeated for each active ingredient,
provided the information is presented in a manner that readily
associates each active ingredient with its purpose (i.e., through the
use of brackets, dot leaders, or other graphical features). The
information described in paragraphs (c)(4) and (c)(6) through (c)(9) of
this section may start on the same line as the required headings. None
of the information described in paragraph (c)(5) of this section shall
appear on the same line as the ``Warning'' or ``Warnings'' heading.
(7) Graphical images (e.g., the UPC symbol) and information not
described in paragraphs (c)(1) through (c)(9) of this section shall not
appear in or in any way interrupt the required title, headings,
subheadings, and information in paragraphs (c)(1) through (c)(9) of
this section. Hyphens shall not be used except to punctuate compound
words.
(8) The information described in paragraphs (c)(1) through (c)(9)
of this section shall be set off in a box or similar enclosure by the
use of a barline. A distinctive horizontal barline extending to each
end of the ``Drug Facts'' box or similar enclosure shall provide
separation between each of the headings listed in paragraphs (c)(2)
through (c)(9) of this section. When a heading listed in paragraphs
(c)(2) through (c)(9) of this section appears on a subsequent panel
immediately after the ``Drug Facts (continued)'' title, a horizontal
hairline shall follow the title and immediately precede the heading. A
horizontal hairline extending within two spaces on either side of the
``Drug
[[Page 13289]]
Facts'' box or similar enclosure shall immediately follow the title and
shall immediately precede each of the subheadings set forth in
paragraph (c)(5) of this section, except the subheadings in paragraphs
(c)(5)(ii)(A) through (c)(5)(ii)(G) of this section.
(9) The information set forth in paragraph (c)(6) of this section
under the heading ``Directions'' shall appear in a table format when
dosage directions are provided for three or more age groups or
populations. The last line of the table may be the horizontal barline
immediately preceding the heading of the next section of the labeling.
(10) If the title, headings, subheadings, and information in
paragraphs (c)(1) through (c)(9) of this section, printed in accordance
with the specifications in paragraphs (d)(1) through (d)(9) of this
section, and any other FDA required information for drug products, and,
as appropriate, cosmetic products, other than information required to
appear on a principle display panel, requires more than 60 percent of
the total surface area available to bear labeling, then the Drug Facts
labeling shall be printed in accordance with the specifications set
forth in paragraphs (d)(10)(i) through (d)(10)(v) of this section. In
determining whether more than 60 percent of the total surface area
available to bear labeling is required, the indications for use listed
under the ``Use(s)'' heading, as set forth in paragraph (c)(4) of this
section, shall be limited to the minimum required uses reflected in the
applicable monograph, as provided in Sec. 330.1(c)(2) of this chapter.
(i) Paragraphs (d)(1), (d)(5), (d)(6), and (d)(7) of this section
shall apply.
(ii) Paragraph (d)(2) of this section shall apply except that the
letter height or type size for the title ``Drug Facts (continued)''
shall be no smaller than 7-point type and the headings in paragraphs
(c)(2) through (c)(9) of this section shall be the larger of either 7-
point or greater type, or 1-point size greater than the point size of
the text.
(iii) Paragraph (d)(3) of this section shall apply except that less
than 0.5-point leading may be used, provided the ascenders and
descenders do not touch.
(iv) Paragraph (d)(4) of this section shall apply except that if
more than one bulleted statement is placed on the same horizontal line,
the additional bulleted statements may continue to the next line of
text, and except that the bullets under each heading or subheading need
not be vertically aligned.
(v) Paragraph (d)(8) of this section shall apply except that the
box or similar enclosure required in paragraph (d)(8) of this section
may be omitted if the Drug Facts labeling is set off from the rest of
the labeling by use of color contrast.
(11)(i) The following labeling outlines the various provisions in
paragraphs (c) and (d) of this section:
BILLING CODE 4160-01-F
[GRAPHIC] [TIFF OMITTED] TR17MR99.003
BILLING CODE 4160-01-C
[[Page 13290]]
(ii) The following sample label illustrates the provisions in
paragraphs (c) and (d) of this section:
[GRAPHIC] [TIFF OMITTED] TR17MR99.004
(iii) The following sample label illustrates the provisions in
paragraphs (c) and (d) of this section, including paragraph (d)(10) of
this section, which permits modifications for small packages:
[GRAPHIC] [TIFF OMITTED] TR17MR99.005
BILLING CODE 4160-01-C
[[Page 13291]]
(iv) The following sample label illustrates the provisions in
paragraphs (c) and (d) of this section for a drug product marketed with
cosmetic claims:
[GRAPHIC] [TIFF OMITTED] TR17MR99.006
BILLING CODE 4160-01-C
(e) Exemptions and deferrals. FDA on its own initiative or in
response to a written request from any manufacturer, packer, or
distributor, may exempt or defer, based on the circumstances presented,
one or more specific requirements set forth in this section on the
basis that the requirement is inapplicable, impracticable, or contrary
to public health or safety. Requests for exemptions shall be submitted
in three copies in the form of an ``Application for Exemption'' to the
Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville,
MD 20852. The request shall be clearly identified on the envelope as a
``Request for Exemption from 21 CFR 201.66 (OTC Labeling Format)'' and
shall be directed to Docket No. 98N-0337. A separate request shall be
submitted for each OTC drug product. Sponsors of a product marketed
under an approved drug application shall also submit a single copy of
the exemption request to their application. Decisions on exemptions and
deferrals will be maintained in a permanent file in this docket for
public review. Exemption and deferral requests shall:
(1) Document why a particular requirement is inapplicable,
impracticable, or is contrary to public health or safety; and
(2) Include a representation of the proposed labeling, including
any outserts, panel extensions, or other graphical or packaging
techniques intended to be used with the product.
(f) Interchangeable terms and connecting terms. The terms listed in
Sec. 330.1(i) of this chapter may be used interchangeably in the
labeling of OTC drug products, provided such use does not alter the
meaning of the labeling that has been established and identified in an
applicable OTC drug monograph or by regulation. The terms listed in
Sec. 330.1(j) of this chapter may be deleted from the labeling of OTC
drug products when the labeling is revised to comply with this section,
provided such deletion does not alter the meaning of the labeling that
has been established and identified in an applicable OTC drug monograph
or by regulation. The terms listed in Sec. 330.1(i) and (j) of this
chapter shall not be used to change in any way the specific title,
headings, and subheadings required under paragraphs (c)(1) through
(c)(9) of this section.
(g) Regulatory action. An OTC drug product that is not in
compliance with the format and content requirements in this section is
subject to regulatory action.
5. Section 201.314 is amended by revising the first two sentences
in paragraph (a) and by revising paragraphs (g)(1) and (h)(1) to read
as follows:
Sec. 201.314 Labeling of drug preparations containing salicylates.
(a) The label of any oral drug preparation intended for sale
without prescription and which contains any salicylate ingredient
(including aspirin, salicylamide, other salicylates, and combinations)
must conspicuously bear, on a clearly contrasting background, the
warning statement: ``Keep out of reach of children [highlighted in bold
type]. In case of overdose, get medical help or contact a Poison
Control Center right away,'' or ``Keep out of reach of children
[highlighted in bold type],'' except that if the article is an aspirin
preparation, it shall bear the first of these warning statements. * * *
* * * * *
(g)(1) The label of any drug containing more than 5 percent methyl
salicylate
[[Page 13292]]
(wintergreen oil) should bear a conspicuous warning such as: ``Do not
use otherwise than as directed.'' These drug products must also include
the ``Keep out of reach of children'' warning and the accidental
ingestion warning as required in Sec. 330.1(g) of this chapter.
* * * * *
(h)(1) The labeling of orally or rectally administered over-the-
counter aspirin and aspirin-containing drug products subject to this
paragraph is required to prominently bear a warning. The warning shall
be as follows: ``Children and teenagers should not use this medicine
for chicken pox or flu symptoms before a doctor is consulted about Reye
syndrome, a rare but serious illness reported to be associated with
aspirin.''
* * * * *
6. Section 201.319 is amended by revising paragraph (b) to read as
follows:
Sec. 201.319 Water-soluble gums, hydrophilic gums, and hydrophilic
mucilloids (including, but not limited to agar, alginic acid, calcium
polycarbophil, carboxymethylcellulose sodium, carrageenan, chondrus,
glucomannan ((B-1,4, linked) polymannose acetate), guar gum, karaya
gum, kelp, methylcellulose, plantago seed (psyllium), polycarbophil,
tragacanth, and xanthan gum) as active ingredients; required warnings
and directions.
* * * * *
(b) Any drug products for human use containing a water-soluble gum,
hydrophilic gum, or hydrophilic mucilloid as an active ingredient in an
oral dosage form when marketed in a dry or incompletely hydrated form
as described in paragraph (a) of this section are misbranded within the
meaning of section 502 of the Federal Food, Drug, and Cosmetic Act
unless their labeling bears the following warnings (under the
subheading ``Choking'') and directions:
```Choking' [highlighted in bold type]: Taking this product
without adequate fluid may cause it to swell and block your throat
or esophagus and may cause choking. Do not take this product if you
have difficulty in swallowing. If you experience chest pain,
vomiting, or difficulty in swallowing or breathing after taking this
product, seek immediate medical attention;'' and
```Directions' [highlighted in bold type]:'' (Select one of the
following, as appropriate: ``Take'' or ``Mix'') ``this product
(child or adult dose) with at least 8 ounces (a full glass) of water
or other fluid. Taking this product without enough liquid may cause
choking. See choking warning.''
* * * * *
7. Appendix A is added to part 201 to read as follows:
Appendix A to Part 201--Examples of Graphic Enhancements Used by FDA
I. Section 201.66 Standard Labeling Format
A. Overall
1. The ``Drug Facts'' labeling is set off in a box or similar
enclosure by the use of a barline with all black type printed on a
white, color contrasting background.
B. Typeface and size
1. ``Drug Facts'' is set in 14 point Helvetica Bold Italic, left
justified.
2. ``Drug Facts (continued)'' is set in 8 point Helvetica Bold
Italic for the words ``Drug Facts'' and 8 point Helvetica Regular
for the word ``(continued)'' and is left justified.
3. The headings (e.g., ``Directions'') are set in 8 point
Helvetica Bold Italic, left justified.
4. The subheadings (e.g., ``Ask a doctor or pharmacist before
use if you are'') are set in 6 point Helvetica Bold, left justified.
5. The information is set in 6 point Helvetica Regular with 6.5
point leading, left justified.
6. The heading ``Purpose'' is right justified.
7. The bullet is a 5 point solid square.
8. Two em spacing separates bullets when more than one bullet is
on the same line.
9. A table format is used for 3 or more dosage directions.
10. A graphic appears at the bottom of the first panel leading
the reader to the next panel.
C. Barlines and hairlines
1. A 2.5-point horizontal barline extends to each end of the
``Drug Facts'' box (or similar enclosure), providing separation
between each of the headings.
2. A 0.5-point horizontal hairline extends within 2 spaces on
either side of the ``Drug Facts'' box (or similar enclosure),
immediately following the title and immediately preceding the
subheadings.
3. A 0.5-point horizontal hairline follows the title,
immediately preceding the heading, when a heading appears on a
subsequent panel immediately after the ``Drug Facts (continued)''
title.
D. Box or Enclosure
1. All information is enclosed by a 2.5-point barline.
II. Section 201.66 Modified Labeling Format
A. Overall
1. The ``Drug Facts'' labeling is presented in all black type
printed on a white color contrasting background.
B. Typeface and size
1. ``Drug Facts'' is set in 9 point Helvetica Bold Italic, left
justified.
2. The headings (e.g., ``Directions'') are set in 8 point
Helvetica Bold Italic, left justified.
3. The subheadings (e.g., ``Ask a doctor or pharmacist before
use if you are'') are set in 6 point Helvetica Bold, left justified.
4. The information is set in 6 point Helvetica Regular with 6.5
point leading, left justified.
5. The heading ``Purpose'' is right justified.
6. The bullet is a 5 point solid square.
7. Bulleted information may start on same line as headings
(except for the ``Warnings'' heading) and subheadings, with 2 em
spacing separating bullets, and need not be vertically aligned.
C. Barlines and hairlines
1. A 2.5-point horizontal barline extends to each end of the
``Drug Facts'' box (or similar enclosure), providing separation
between each of the headings.
2. A 0.5-point horizontal hairline extends within 2 spaces on
either side of the ``Drug Facts'' box (or similar enclosure),
immediately following the title and immediately preceding the
subheadings.
D. Box or Enclosure
1. All information is set off by color contrast. No barline is
used.
BILLING CODE 4160-01-F
[[Page 13293]]
III. Examples of Sec. 201.66 Standard Labeling and Modified Labeling
Formats
A. Section 201.66 Standard Labeling Format
[GRAPHIC] [TIFF OMITTED] TR17MR99.007
B. Section 201.66 Modified Labeling Format
[GRAPHIC] [TIFF OMITTED] TR17MR99.008
BILLING CODE 4160-01-C
[[Page 13294]]
PART 330--OVER-THE-COUNTER (OTC) HUMAN DRUGS WHICH ARE GENERALLY
RECOGNIZED AS SAFE AND EFFECTIVE AND NOT MISBRANDED
8. The authority citation for 21 CFR part 330 continues to read as
follows:
Authority: 21 U.S.C. 321, 351, 352, 353, 355, 360, 371.
9. Section 330.1 is amended by revising paragraphs (c)(1), (c)(2),
(i), and (j), and by removing the first three sentences in paragraph
(g) and adding two sentences in their place to read as follows:
Sec. 330.1 General conditions for general recognition as safe,
effective, and not misbranded.
* * * * *
(c)(1) The product is labeled in compliance with chapter V of the
Federal Food, Drug, and Cosmetic Act (the act) and subchapter C et seq.
of this chapter, including the format and content requirements in
Sec. 201.66 of this chapter. An OTC drug product that is not in
compliance with chapter V and subchapter C, including Sec. 201.66 of
this chapter, is subject to regulatory action. For purposes of
Sec. 201.61(b) of this chapter, the statement of identity of the
product shall be the term or phrase used in the applicable OTC drug
monograph established in this part.
(2) The ``Uses'' section of the label and labeling of the product
shall contain the labeling describing the ``Indications'' that have
been established in an applicable OTC drug monograph or alternative
truthful and nonmisleading statements describing only those indications
for use that have been established in an applicable monograph, subject
to the provisions of section 502 of the act relating to misbranding and
the prohibition in section 301(d) of the act against the introduction
or delivery for introduction into interstate commerce of unapproved new
drugs in violation of section 505(a) of the act. Any other labeling
under this subchapter and subchapter C et seq. of this chapter shall be
stated in the exact language where exact language has been established
and identified by quotation marks in an applicable OTC drug monograph
or by regulation (e.g., Sec. 201.63 of this chapter), except as
provided in paragraphs (i) and (j) of this section.
* * * * *
(g) The labeling for all drugs contains the general warning: ``Keep
out of reach of children.'' [highlighted in bold type]. The labeling of
drugs shall also state as follows: For drugs used by oral
administration, ``In case of overdose, get medical help or contact a
Poison Control Center right away''; for drugs used topically, rectally,
or vaginally and not intended for oral ingestion, ``If swallowed, get
medical help or contact a Poison Control Center right away''; and for
drugs used topically and intended for oral use, ``If more than used
for'' (insert intended use, e.g., pain) ``is accidentally swallowed,
get medical help or contact a Poison Control Center right away.'' * * *
* * * * *
(i) The following terms may be used interchangeably in the labeling
of OTC drug products, provided such use does not alter the meaning of
the labeling that has been established and identified in an applicable
monograph or by regulation. The following terms shall not be used to
change in any way the title, headings, and subheadings required under
Sec. 201.66(c)(1) through (c)(9) of this chapter:
(1) ``Abdominal'' or ``stomach'' (in context only).
(2) ``Administer'' or ``give''.
(3) ``Aggravate(s)'' or ``make(s) worse''.
(4) ``Application of this product'' or ``applying''.
(5) ``Are uncertain'' or ``do not know''.
(6) ``Ask'' or ``consult'' or ``contact''.
(7) ``Asking'' or ``consulting''.
(8) ``Assistance'' or ``help'' or ``aid''.
(9) ``Associated with'' or ``due to'' or ``caused by''.
(10) ``Avoid contact with eyes'' or ``do not get into eyes''.
(11) ``Avoid inhaling'' or ``do not inhale''.
(12) ``Before a doctor is consulted'' or ``without first consulting
your doctor'' or ``consult your doctor before''.
(13) ``Beverages'' or ``drinks''.
(14) ``Clean'' or ``cleanse''.
(15) ``Consulting'' or ``advising''.
(16) ``Continue(s)'' or ``persist(s)'' or ``is persistent'' or
``do(es) not go away'' or ``last(s)''.
(17) ``Daily'' or ``every day''.
(18) ``Develop(s)'' or ``begin(s)'' or ``occur(s)''.
(19) ``Difficulty'' or ``trouble''.
(20) ``Difficulty in urination'' or ``trouble urinating''.
(21) ``Discard'' or ``throw away''.
(22) ``Discontinue'' or ``stop'' or ``quit''.
(23) ``Doctor'' or ``physician''.
(24) ``Drowsiness'' or ``the drowsiness effect''.
(25) ``Drowsiness may occur'' or ``you may get drowsy''.
(26) ``Enlargement of the'' or ``an enlarged''.
(27) ``Especially in children'' or especially children''.
(28) ``Exceed'' or ``use more than'' or ``go beyond''.
(29) ``Exceed recommended dosage'' or ``use more than directed''.
(30) ``Excessive'' or ``too much''.
(31) ``Excitability may occur'' or ``you may get excited''.
(32) ``Experience'' or ``feel''.
(33) ``For relief of'' or ``relieves''.
(34) ``For temporary reduction of'' or ``temporarily reduces''.
(35) ``For the temporary relief of'' or ``temporarily relieves''.
(36) ``For the treatment of'' or ``treats''.
(37) ``Frequently'' or ``often''.
(38) ``Give to'' or ``use in''.
(39) ``Immediately'' or ``right away'' or ``directly''.
(40) ``Immediately'' or ``as soon as''.
(41) ``Immediately following'' or ``right after''.
(42) ``Improve(s)'' or ``get(s) better'' or ``make(s) better''.
(43) ``Increased'' or ``more''.
(44) ``Increase your risk of'' or ``cause''.
(45) ``Indication(s)'' or ``Use(s)''.
(46) ``Inhalation'' or ``puff''.
(47) ``In persons who'' or ``if you'' or ``if the child''.
(48) ``Instill'' or ``put''.
(49) ``Is (are) accompanied by'' or ``you also have'' (in context
only) or ``(optional: that) occur(s) with''.
(50) ``Longer'' or ``more''.
(51) ``Lung'' or ``pulmonary''.
(52) ``Medication(s)'' or ``medicine(s)'' or ``drug(s)''.
(53) ``Nervousness, dizziness, or sleeplessness occurs'' or ``you
get nervous, dizzy, or sleepless''.
(54) ``Not to exceed'' or ``do not exceed'' or ``not more than''.
(55) ``Obtain(s)'' or ``get(s)''.
(56) ``Passages'' or ``passageways'' or ``tubes''.
(57) ``Perforation of'' or ``hole in''.
(58) ``Persistent'' or ``that does not go away'' or ``that
continues'' or ``that lasts''.
(59) ``Per day'' or ``daily''.
(60) ``Presently'' or ``now''.
(61) ``Produce(s)'' or ``cause(s)''.
(62) ``Prompt(ly)'' or ``quick(ly)'' or ``right away''.
(63) ``Reduce'' or ``minimize''.
(64) ``Referred to as'' or ``of''.
(65) ``Sensation'' or ``feeling''.
(66) ``Solution'' or ``liquid''.
(67) ``Specifically'' or ``definitely''.
(68) ``Take'' or ``use'' or ``give''.
(69) ``Tend(s) to recur'' or ``reoccur(s)'' or ``return(s)'' or
``come(s) back''.
(70) ``To avoid contamination'' or ``avoid contamination'' or ``do
not contaminate''.
(71) ``To help'' or ``helps''.
(72) ``Unless directed by a doctor'' or ``except under the advice
of a doctor'' or ``unless told to do so by a doctor''.
[[Page 13295]]
(73) ``Use caution'' or ``be careful''.
(74) ``Usually'' or ``generally'' (in context only).
(75) ``You'' (``Your'') or ``the child'' (``the child's'').
(76) ``You also have'' or ``occurs with''.
(77) ``When practical'' or ``if possible''.
(78) ``Whether'' or ``if''.
(79) ``Worsen(s)'' or ``get(s) worse'' or ``make(s) worse''.
(j) The following connecting terms may be deleted from the labeling
of OTC drug products, provided such deletion does not alter the meaning
of the labeling that has been established and identified in an
applicable monograph or by regulation. The following terms shall not be
used to change in any way the specific title, headings, and subheadings
required under Sec. 201.66(c)(1) through (c)(9) of this chapter:
(l) ``And''.
(2) ``As may occur with''.
(3) ``Associated'' or ``to be associated''.
(4) ``Consult a doctor''.
(5) ``Discontinue use''.
(6) ``Drug Interaction Precaution''.
(7) ``Due to''.
(8) ``Except under the advice and supervision of a physician''.
(9) ``If this occurs''.
(10) ``In case of''.
(11) ``Notice''.
(12) ``Or''.
(13) ``Occurring with''.
(14) ``Or as directed by a doctor''.
(15) ``Such as''.
(16) ``Such as occurs with''.
(17) ``Tends to''.
(18) ``This product''.
(19) ``Unless directed by a doctor''.
(20) ``While taking this product'' or ``before taking this
product''.
(21) ``Within''.
* * * * *
PART 331--ANTACID PRODUCTS FOR OVER-THE-COUNTER (OTC) HUMAN USE
10. The authority citation for 21 CFR part 331 continues to read as
follows:
Authority: 21 U.S.C. 321, 351, 352, 353, 355, 360, 371.
11. Section 331.30 is amended by revising paragraph (d) to read as
follows:
Sec. 331.30 Labeling of antacid products.
* * * * *
(d) Drug interaction precaution. The labeling of the product
contains the following statement ``Ask a doctor or pharmacist before
use if you are [bullet]\1\ presently taking a prescription drug.
Antacids may interact with certain prescription drugs.''
---------------------------------------------------------------------------
\1\ See Sec. 201.66(b)(4) of this chapter.
---------------------------------------------------------------------------
* * * * *
PART 341--COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC
DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE
12. The authority citation for 21 CFR part 341 continues to read as
follows:
Authority: 21 U.S.C. 321, 351, 352, 353, 355, 360, 371.
13. Section 341.74 is amended by revising paragraphs (c)(4)(v) and
(c)(4)(vi) to read as follows:
Sec. 341.74 Labeling of antitussive drug products.
* * * * *
(c) * * *
(4) * * *
(v) For products containing dextromethorphan or dextromethorphan
hydrobromide as identified in Sec. 341.14(a)(3) and (a)(4) when labeled
for adults or for adults and children under 12 years of age. Drug
interaction precaution. ``Do not use if you are now taking a
prescription monoamine oxidase inhibitor (MAOI) (certain drugs for
depression, psychiatric, or emotional conditions, or Parkinson's
disease), or for 2 weeks after stopping the MAOI drug. If you do not
know if your prescription drug contains an MAOI, ask a doctor or
pharmacist before taking this product.''
(vi) For products containing dextromethorphan or dextromethorphan
hydrobromide as identified in Sec. 341.14(a)(3) and (a)(4) when labeled
only for children under 12 years of age. Drug interaction precaution.
``Do not give to a child who is taking a prescription monoamine oxidase
inhibitor MAOI) (certain drugs for depression, psychiatric, or
emotional conditions, or Parkinson's disease), or for 2 weeks after
stopping the MAOI drug. If you do not know if your child's prescription
drug contains an MAOI, ask a doctor or pharmacist before giving this
product.''
* * * * *
14. Section 341.76 is amended by revising paragraph (c)(4) to read
as follows:
Sec. 341.76 Labeling of bronchodilator drug products.
* * * * *
(c) * * *
(4) Drug interaction precaution. ``Do not use if you are now taking
a prescription monoamine oxidase inhibitor (MAOI) (certain drugs for
depression, psychiatric, or emotional conditions, or Parkinson's
disease), or for 2 weeks after stopping the MAOI drug. If you do not
know if your prescription drug contains an MAOI, ask a doctor or
pharmacist before taking this product.''
* * * * *
15. Section 341.80 is amended by revising paragraphs (c)(1)(i)(D)
and (c)(1)(ii)(D) to read as follows:
Sec. 341.80 Labeling of nasal decongestant drug products.
* * * * *
(c) * * *
(1) * * *
(i) * * *
(D) Drug interaction precaution. ``Do not use if you are now taking
a prescription monoamine oxidase inhibitor (MAOI) (certain drugs for
depression, psychiatric, or emotional conditions, or Parkinson's
disease), or for 2 weeks after stopping the MAOI drug. If you do not
know if your prescription drug contains an MAOI, ask a doctor or
pharmacist before taking this product.''
(ii) * * *
(D) Drug interaction precaution. ``Do not give to a child who is
taking a prescription monoamine oxidase inhibitor (MAOI) (certain drugs
for depression, psychiatric, or emotional conditions, or Parkinson's
disease), or for 2 weeks after stopping the MAOI drug. If you do not
know if your child's prescription drug contains an MAOI, ask a doctor
or pharmacist before giving this product.''
* * * * *
PART 346--ANORECTAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE
16. The authority citation for 21 CFR part 346 continues to read as
follows:
Authority: 21 U.S.C. 321, 351, 352, 353, 355, 360, 371.
17. Section 346.50 is amended by revising paragraph (c)(7)(ii) to
read as follows:
Sec. 346.50 Labeling of anorectal drug products.
* * * * *
(c) * * *
(7) * * *
(ii) ``Ask a doctor or pharmacist before use if you are [bullet]\1\
presently taking a prescription drug for high blood pressure or
depression.''
---------------------------------------------------------------------------
\1\ See Sec. 201.66(b)(4) of this chapter.
---------------------------------------------------------------------------
* * * * *
[[Page 13296]]
PART 355--ANTICARIES DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE
18. The authority citation for 21 CFR part 355 continues to read as
follows:
Authority: 21 U.S.C. 321, 351, 352, 353, 355, 360, 371.
19. Section 355.50 is amended by revising paragraphs (c)(1) and
(c)(2) to read as follows:
Sec. 355.50 Labeling of anticaries drug products.
* * * * *
(c) * * *
(1) For all fluoride dentifrice (gel, paste, and powder) products.
``Keep out of reach of children under 6 years of age. [highlighted in
bold type] If more than used for brushing is accidentally swallowed,
get medical help or contact a Poison Control Center right away.'' These
warnings shall be used in place of the general warning statements
required by Sec. 330.1(g) of this chapter.
(2) For all fluoride rinse and preventive treatment gel products.
``Keep out of reach of children. [highlighted in bold type] If more
than used for'' (select appropriate word: ``brushing'' or ``rinsing'')
``is accidentally swallowed, get medical help or contact a Poison
Control Center right away.'' These warnings shall be used in place of
the general warning statements required by Sec. 330.1(g) of this
chapter.
* * * * *
PART 358--MISCELLANEOUS EXTERNAL DRUG PRODUCTS FOR OVER-THE-COUNTER
HUMAN USE
20. The authority citation for 21 CFR part 358 continues to read as
follows:
Authority: 21 U.S.C. 321, 351, 352, 353, 355, 360, 371.
21. Section 358.650 is amended in paragraph (d)(1) by revising the
information in the brackets to read as follows:
Sec. 358.650 Labeling of pediculicide drug products.
* * * * *
(d) * * *
(1) * * * [statement in boldface type].
* * * * *
PART 369--INTERPRETATIVE STATEMENTS RE WARNINGS ON DRUGS AND
DEVICES FOR OVER-THE-COUNTER SALE
22. The authority citation for 21 CFR part 369 continues to read as
follows:
Authority: 21 U.S.C. 321, 331, 351, 352, 353, 355, 371.
23. Section 369.9 is revised to read as follows:
Sec. 369.9 General warnings re accidental ingestion by children.
Section 369.20 includes under certain items, but not all medicines,
the statement: ``Keep this and all medicines out of children's reach.
In case of overdose, get medical help or contact a Poison Control
Center right away,'' or ``Keep out of reach of children.'' However, in
view of the possibility of accidental ingestion of drugs, it is not
only suggested but is recommended that one of these statements be used
on the label of all drug products.
Sec. 369.20 Drugs; recommended warning and caution statements.
[Amended]
24. Section 369.20 is amended as follows:
a. The entry ``NUX VOMICA AND STRYCHNINE PREPARATIONS.'' is revised
to read as follows:
NUX VOMICA AND STRYCHNINE PREPARATIONS.
``Do not use more than the recommended dosage. Keep out of reach of
children. In case of overdose, get medical help or contact a Poison
Control Center right away.''
b. The entry beginning ``SALICYLATES, INCLUDING ASPIRIN'' is
revised to read as follows:
SALICYLATES, INCLUDING ASPIRIN AND SALICYLAMIDE (EXCEPT METHYL
SALICYLATE, EFFERVESCENT SALICYLATE PREPARATIONS, AND PREPARATIONS OF
AMINOSALICYLIC ACID AND ITS SALTS). (See also Sec. 201.314 of this
chapter.)
``Keep out of reach of children. In case of overdose, get medical
help or contact a Poison Control Center right away;'' or ``Keep out of
reach of children.''
If the article is an aspirin preparation, it should bear the first
of the above two warning statements. In either case, the above
information should appear on the label.
Caution--For children under 3 years of age, consult your physician;
or
Caution--For younger children, consult your physician.
One of the two immediately preceding caution statements is required
on the label of all aspirin tablets, but such a statement is not
required on the labels of other salicylates clearly offered for
administration to adults only.
If offered for use in arthritis or rheumatism, in juxtaposition
therewith, the statement:
Caution--If pain persists for more than 10 days, or redness is
present, or in conditions affecting children under 12 years of age,
consult a physician immediately.
c. The entry ``SALICYLATES: METHYL SALICYLATE (WINTERGREEN OIL).''
is revised to read as follows:
SALICYLATES: METHYL SALICYLATE (WINTERGREEN OIL). (See also
Secs. 201.303 and 201.314 of this chapter.)
``Do not use otherwise than as directed. Keep out of reach of
children to avoid accidental poisoning. If swallowed, get medical help
or contact a Poison Control Center right away.''
If the preparation is a counter-irritant or rubefacient the
statement:
Caution--Discontinue use if excessive irritation of the skin
develops. Avoid getting into the eyes or on mucous membranes.
If offered for use in arthritis or rheumatism, in juxtaposition
therewith, the statement:
Caution--If pain persists for more than 10 days, or redness is
present, or in conditions affecting children under 12 years of age
consult a physician immediately.
d. The entry ``ZINC STEARATE DUSTING POWDERS.'' is revised to read
as follows:
ZINC STEARATE DUSTING POWDERS.
``Keep out of reach of children; avoid inhaling. If swallowed, get
medical help or contact a Poison Control Center right away.''
Sec. 369.21 Drugs; warning and caution statements required by
regulations. [Amended]
25. Section 369.21 is amended as follows:
a. The entry ```COUGH-DUE-TO-COLD' PREPARATIONS (CARBETAPENTANE
CITRATE).'' is revised to read as follows:
``COUGH-DUE-TO-COLD'' PREPARATIONS (CARBETAPENTANE CITRATE). (See
Sec. 310.201(a)(20) of this chapter.)
``Keep out of reach of children. In case of overdose, get medical
help or contact a Poison Control Center right away.''
b. The entry ``SODIUM GENTISATE.'' is revised to read as follows:
SODIUM GENTISATE. (See Secs. 201.314 and 310.301(a)(2) of this
chapter.)
Warning--Do not give to children under 6 years of age or use for
prolonged period unless directed by physician.
``Keep out of reach of children. In case of overdose, get medical
help or contact a Poison Control Center right away.''
If offered for use in arthritis or rheumatism, in juxtaposition
therewith, the statement:
Caution--If pain persists for more than 10 days, or redness is
present, or
[[Page 13297]]
in conditions affecting children under 12 years of age, consult a
physician immediately.
PART 701--COSMETIC LABELING
26. The authority citation for 21 CFR part 701 continues to read as
follows:
Authority: 21 U.S.C. 321, 352, 361, 362, 363, 371, 374; 15
U.S.C. 1454, 1455.
27. Section 701.3 is amended by revising paragraph (d) to read as
follows:
Sec. 701.3 Designation of ingredients.
* * * * *
(d) Where a cosmetic product is also an over-the-counter drug
product, the declaration shall declare the active drug ingredients as
set forth in Sec. 201.66(c)(2) and (d) of this chapter, and the
declaration shall declare the cosmetic ingredients as set forth in
Sec. 201.66(c)(8) and (d) of this chapter.
* * * * *
Dated: January 4, 1999.
Jane E. Henney
Commissioner of Food and Drugs.
Donna E. Shalala,
Secretary of Health and Human Services.
Note: The following Appendix A to the preamble will not appear
in the Code of Federal Regulations.
BILLING CODE 4160-01-F
Appendix A to Preamble--Examples of Prototype OTC Drug Product Labeling
[GRAPHIC] [TIFF OMITTED] TR17MR99.009
[[Page 13298]]
[GRAPHIC] [TIFF OMITTED] TR17MR99.010
[[Page 13299]]
[GRAPHIC] [TIFF OMITTED] TR17MR99.011
[[Page 13300]]
[GRAPHIC] [TIFF OMITTED] TR17MR99.012
[[Page 13301]]
[GRAPHIC] [TIFF OMITTED] TR17MR99.013
[[Page 13302]]
[GRAPHIC] [TIFF OMITTED] TR17MR99.014
[[Page 13303]]
[GRAPHIC] [TIFF OMITTED] TR17MR99.015
[FR Doc. 99-6296 Filed 3-11-99; 11:59 am]
BILLING CODE 4160-01-C
This is a copy of a public record, reproduced as it was published. It is not legal advice, and it may not be the version a court would rely on. Check the official source before you cite it.