**[Supporting Statement]{.underline}**

OTC Human Drugs; for Labeling Requirements

OMB Control Number 0910-0340

Docket Number 010398

A. **[Justification]{.underline}**

1\. [Circumstances Necessitating Information Collection.]{.underline}

The Food and Drug Administration (FDA) regulations governing labeling
requirements for human over-the-counter (OTC) drug products provide for
a standardized content and format for all products. The outside
container or wrapper of the retail package ( or the immediate container
label if there is no outside container or wrapper) of all OTC drug
products contains uniform headings and subheadings, presented in a
standardized order, with standards for type size and other graphical
features. The requirements are intended to enable consumers to better
read and understands OTC drug product labeling and to apply this
information to the safe and effective use of OTC drug products.

FDAs legal authority for these labeling requirements derives from
sections 201, 502, 505, 507, and 701 of the Federal Food, Drug and
Cosmetic Act (21 U.S.C. 321, 352, 355, 357, and 371.). Regulating the
content of OTC drug product labeling is consistent with FDA\'s authority
to ensure that the products are safe and effective for use (21 U.S.C.
321 (n), 321 (p), 352, 355, and 357). Regulating the order, appearance,
and format of OTC drug product labeling is consistent with FDA's
authority to ensure that drug labeling convey all material information
to the consumer (21 U.S.C. 321 (n) and 352(a)), and that labeling
communicate this information in a manner that is "likely to be read and
understood by the ordinary individual under customary conditions of
purchase and use" (21 U.S.C. 352(c)).

Section 201.66 requires all OTC manufacturers to format labeling as set
forth in subsections (c) and (d). FDA has learned from the industry that
OTC manufacturers routinely redesign the labeling of OTC products as
part of their usual and customary business practice. This rule provides
varied time frames for implementing the OTC labeling requirements.
Therefore, the majority of respondents will be able to format OTC
labeling in accordance with 201.66 as part of their routine redesign
practice, creating no additional paperwork or economic burden. However,
of the 39,310 SKUs currently under a final monograph, FDA has determined
that approximately 32 percent, or 12, 572 products, may necessitate
labeling format changes sooner than provided under their usual and
customary practice of label redesign. FDA has estimated that of the 400
respondents who produce OTC products, including the 12, 572 products
described above, each may be required to respond approximately 31.4
times to this rule outside of their usual and customary practice. Each
response is estimated to take, on the average, 4 hours, for a total of
50,288 hours per year. This burden is expected to be a one-time burden.

Although the usual and customary practice of label redesign will
minimize the burden for the remaining 68 percent of SKUs currently
marketed, or 26,720 products, additional time may be necessary for each
company to make the format changes under this rule. FDA has estimated
that of the 400 respondents, who produce OTC products, each may be
required to respond approximately 66.8 times to bring the 26,720
products into compliance with this rule. FDA estimates that for this
group, each response will take an average of 2.5 hours for a total of
66,800 hours. This is expected to be a one time burden. The chart
reflects this group on the second line.

Under 21 CFR 201.66 (e), respondents subject to this rule are required
to submit requests in writing for exemptions and deferrals from the
specific requirements of 21 CFR 201.66. Based on its experience with
exemption and deferral requests under similar provisions, FDA estimates
that approximately 16% of the total number of respondents, or 25
manufacturers, packers, or distributors, are likely to submit such
requests on the average of one time per year. Such requests take an
average of 24 hours each for a total of 2,400 hours annually.

Section 201.66 of the labeling requirements (21 CFR 201.66) requires all
OTC drug manufacturers to format labeling as set forth in subsections
(c) and (d). FDA has learned from the industry that OTC drug product
manufacturers routinely redesign the labeling of their products as part
of their usual and customary business practice. The rule provides varied
timeframes for implementing the labeling requirements. Therefore, the
majority of respondents will be able to format OTC drug product labeling
in accordance with §201.66 as part of their routine redesign practice,
creating no additional paperwork or economic burden.

2\. [How, By whom, and for What Purpose]{.underline}

The purpose of this rule is to maintain a standardized format for the
labeling of all OTC drug products so that the labeling will be clear,
simple, and easier to read. Variability in the design, format, and
placement of required OTC drug product labeling information make it
difficult for consumers to find and read important information. In order
for consumers to safely and effectively use OTC drug products, important
labeling information is readily accessible, readable, and easily
understood. If information is not processed or is ignored due to factors
affecting readability, such as small print size, OTC drugs cannot be
used safely and effectively. Nevertheless, technical information such as
warnings, cautions, and contraindications, is often presented in small
print. Moreover, variability in the design, format, and placement of
required OTC drug product labeling information make it difficult for
consumers to both find and read safety information, it must not only be
readily accessible, but it must also be readable, readily understood,
noted, and acted upon. If information is not processed or is ignored due
to factors affecting readability, such as small print size, it cannot
provide the health benefits that would result from the safe and
effective use of OTC drug products. Nevertheless, warnings, cautions,
and contraindications, which are relatively technical, are often
presented in small print. Moreover, the amount of information and the
lack of uniform presentation of that information currently found on OTC
drug product labels make it difficult to compare labels. The variability
of such information may lead to market inefficiencies that include
suboptimal purchases, inappropriate price-quality relationships, and
competitive inefficiencies. The agency believes that standardized
labeling format, minimum print size, and consistent text enhances
consumers ability to find and read relevant safety information.
Potential benefits include easier product comparison, improved consumer
decision making and self-treatment, and fewer adverse drug experiences.

3\. [Considerations of Information Technology]{.underline}

Previously, FDA began working with pharmaceutical sponsors to develop
Computer-Assisted New Drug Applications (CANDA). CANDAs were designed to
provide information (text, data, and image) electronically to facilitate
the review of applications (including the submission of information
required under this collection of information, such as labeling
supplements and amendments). These efforts yielded valuable information
but were limited because for each new drug review division sponsors
tended to develop different hardware and software approaches. A reviewer
might be confronted with an array of hardware, software, and review
tools to conduct a review that differed between sponsors and
applications. Also, CANDAs were never approved as a substitute for the
archival copy, so firms were still required to submit copies.

One solution to limitations of CANDAs was an approach whereby staff
responsible for a particular review discipline (e.g., chemistry,
clinical) worked directly with pharmaceutical sponsors to develop a
consistent approach that would be applicable to all sponsors and to all
review divisions. Focus on this approach has evolved into the Electronic
Regulatory Submission and Review (ERSR) Program. This new initiative is
intended to ensure both the electronic availability of information and
the means to manipulate this information electronically to yield a
review.

ERSR has been made possible by other developments. The harmonization of
FDA Form 356h has ensured that NDAs, ANDAs, and Biological License
Applications (BLAs) would contain comparable information in the same
sections of the submission. The promulgation of the Electronic Records;
Electronic Signatures final rule allowed FDA to accept electronic
submissions without an accompanying paper archival copy because
electronic records are equivalent to paper records and electronic
signatures are equivalent to hand-written signatures provided the
requirements of 21 CFR Part 11 are met and the document has been
identified in the agencys public docket as being acceptable for filing.
The Guidance for Industry on :Archiving Submissions in Electronic
Format - NDAs provides for the receipt and archival of electronic report
forms and tabulations. Another Guidance for Industry entitled Providing
Regulatory Submissions in Electronic Format - NDAs is currently under
development.

ERSR is made up of a variety of projects that are in different stages of
development and implementation. These projects are categorized into 3
areas: First, Electronic Submissions includes standards-related projects
to define the format and content of regulatory submissions; written
guidance for industry to follow in preparing electronic submissions; and
Electronic Document Room project to accommodate the receipt, archive,
and storage of electronic transmissions; an Electronic Gateway project
to provide an agency-level central point for receipt of secure
electronic transmissions and routing to the Centers; and scientific
databases that include structured databases, reference guides, and
analytical tools used by reviewers. Second, Corporate Databases,
Documentbases and Applications includes projects under the Electronic
Document Management System and the Management Information System. Third,
other electronic initiatives include technical infrastructure, technical
support, and training.

ERSR will impact the underlying business processes related to regulatory
submissions and reviews. Document rooms will handle electronic media
rather than paper copies. Reviewers will review submissions online and
generate their review documents online. Reviewers will conduct data
analysis using structured databases, which combine data extracted from
the submission under review as well as historical data from earlier
submissions. Industry sponsors and manufacturers will experience reduced
paper costs and manpower to compile paper submissions and better access
to application status information through electronic mail.

4.  [Identification of Duplication]{.underline}

The reporting required does not duplicate any other information
collection. This reporting is the only practical means available to FDA
to ensure that the labeling of OTC drugs subject to an approved
application comply with the new format and content requirements.

5\. [Small Businesses]{.underline}

Steps the agency has taken to minimize the impact on small entities
include: (1) Provide enough time for implementation to enable entities
to use up existing label stock, (2) provide sufficient time to
coordinate a substantial proportion of the label changes with routine
industry-initiated labeling changes, (3) provide a mechanism for
applying for an exemption or a deferral (when the requirements are
judged inapplicable, impracticable, or unnecessary), and (4) provide an
additional year to comply for individual OTC drug products having sales
of less than \$25,000. This additional year for reduces total industry
costs by \$5.5million. While this last provision extending the
compliance time provides flexibility for a substantial number of
individual OTC drug products ( about 40 percent), the impact on overall
retail sales is negligible (less than 1 percent) These actions provide
substantial flexibility and reductions in cost for small entities.

6\. [Consequences of Less Frequent Information Collection and Technical
or Legal Obstacles.]{.underline}

FDA would be unable to determine, before an OTC product is available to
consumers, whether the labeling complies with the revised format and
content requirements.

7\. [Inconsistencies with 5 CFR 1320.6 or Special
Circumstances]{.underline}

> Data collection for applications is consistent with all the
> requirements of section 1320.6.

8\. [Consultations with outside Sources]{.underline}

> During the past several years, many consumers have written to FDA to
> express concern about the legibility and understandability of OTC drug
> product labeling. Many individuals, especially the elderly, are
> concerned with small print size, print style, and lack of color
> contrast. Consumers stated that poor labeling legibility may cause
> them to select an improper dose, and this may result in adverse drug
> reactions. Consumers have also submitted comments to FDA about the
> print size of OTC drug product labeling in response to various OTC
> drug product rulemakings.
>
> The new labeling requirements resulted from a public rulemaking in
> which over 1,800 comments were received form consumers, Congressional
> representatives, professional organizations, manufacturers, health
> professionals, health departments, universities, and trade
> associations. Following issuance of the final rule, FDA met with trade
> associations, individual manufacturers, and other interested parties
> to discuss implementation of the new labeling requirements. One result
> of these meetings was an extension of the May 16, 2001 compliance date
> by one year to May 16, 2002 (with a corresponding extension from May
> 16, 2002 to May 16, 2003 for products with annual sales of less than
> \$25,000).

In the Federal Register of September 27, 2001, (66 FR 49388), the agency
requested comments on the proposed collection of information, No
comments were received.

9\. [Payments or gifts to Respondents]{.underline}

FDA has not provided and has no intention to provide any payment or gift
to respondents under these labeling requirements.

10\. [Confidentiality of Information]{.underline}

The reporting requirements have no confidentiality implications.

11\. [Sensitive Questions]{.underline}

There are no questions of a sensitive nature.

12\. [Total Hour Burden to Respondents]{.underline}

The agency believes the hours per response and total hours may be less
than the numbers stated in the final rule for several reasons. First,
respondents have made a number of inquiries already since the final rule
was issued in 1999. The agency\'s experience with these inquires made to
the agency is that inquiries have been less than 2.5 or 4 hours per
response, generally averaging 0.25 to 0.5 hours per inquiry. Second, the
agency issued a draft guidance for industry entitled \"Labeling
Over-The-Counter Human Drug Products; Updating Labeling in ANDA\'s\" (66
FR 11174, February 22, 2001), which included a number of labeling
examples to assist holders of ANDA\'s for OTC drug products and
manufacturers of reference listed drugs for the ANDA\'s to implement the
new OTC drug product labeling regulation. This guidance should have
reduced some of the hours per response and total hours for some NDA and
ANDA holders. However, the agency is not currently able to estimate how
much the time has been reduced. Accordingly, the agency is listing the
same hours per response and total hours in this notice as appeared in
the final rule.

FDA estimates the burden of this collection of information as follows:

TABLE 1.\--Estimated Annual Reporting Burden

  --------------------------------------------------------------------------
  Estimated                                                      
  Annual                                                         
  Reporting                                                      
  Burden                                                         
  ------------ ------------- ----------- ----------- ----------- -----------
  21 CFR       Number of     Annual      Total       Hours Per   Total Hours
  Section      Respondents   Frequency   Annual      Response    
                             per         Responses               
                             Response                            

  201.66[^1]   400           31.43       12,572      4           50, 288

  201.66       400           66.8        26,720      2.5         66,800

  201.66 (c),  61            8.5         518         2           1,037
  (d)[^2]                                                        

  201.66(e)    25            4           100         24          2,400

  Total                                                          120,525
  --------------------------------------------------------------------------

Operating and Maintenance Costs Associated with this Information
Collection

One-time burden.

13\. [Total Annual Cost Burden to Respondents]{.underline}

Based on an hourly industry cost of \$100 (wages plus overhead), the
total cost burden to respondents would be \$5, 373,600 (53, 736 X
\$100).

14\. [Annualized Cost to FDA]{.underline}

FDA estimates that it would take application reviewers approximately 30
minutes to review supplements and amendments and other revised labeling
submissions. Based on a hourly cost to FDA of \$100 (wages plus
overhead), and based on a total of 13,195 submissions, the total cost to
FDA would be \$ 1, 319,500.

15\. [Changes in Burden]{.underline}

The reporting burden for the extension of this information collection,
Format and Content Requirements for OTC Drug Labeling has not changed
from that in the approved final rule.

16\. [Publication of Information Collection Results/Statistical
Reporting]{.underline}

FDA does not intend to publish tabulated results of the information
collection requirements that would be imposed by these regulations.

17\. [Display of OMB Expiration Date on Form Approval Date]{.underline}

There are no forms associated with this collection.

18\. [Exceptions to Certification Statement.\"]{.underline}

There are no exceptions to the certification statement identified in
Item 19, Certification for Paperwork Reduction Act Submission, of OMB
Form 83-I.

[^1]:

[^2]: