Notice: Agency Information Collection Activities; Proposed Collection; 
Comment Request; Requirements on Content and Format of Labeling for 
Human Prescription Drug and Biological Products

Federal Register: September 29, 2008 (Volume 73, Number 189)            
                  Page 56592-56595

AGENCY:  Food and Drug Administration, HHS.

ACTION:  Notice.

SUMMARY:  The Food and Drug Administration (FDA) is announcing an 
opportunity for public comment on the proposed collection of certain 
information by the agency. Under the Paperwork Reduction Act of 1995 
(the PRA), Federal agencies are required to publish notice in the 
Federal Register concerning each proposed collection of information, 
including each proposed extension of an existing collection of 
information, and to allow 60 days for public comment in response to the

[[Page 56593]]

notice. This notice solicits comments on the information collection 
provisions of FDA's requirements on content and format of labeling for 
human prescription drug and biological products.

DATES:  Submit written or electronic comments on the collection of 
information by November 28, 2008.

ADDRESSES:  Submit electronic comments on the collection of information 
to http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.regulations.gov. 
Submit written comments on the 
collection of information to the Division of Dockets Management (HFA-
305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, 
Rockville, MD 20852. All comments should be identified with the docket 
number found in brackets in the heading of this document.

FOR FURTHER INFORMATION CONTACT:  Elizabeth Berbakos, Office of 
Information Management (HFA-710), Food and Drug Administration, 5600 
Fishers Lane, Rockville, MD 20857, 301-796-3792.

SUPPLEMENTARY INFORMATION: Under the PRA (44 U.S.C. 3501-3520), Federal 
agencies must obtain approval from the Office of Management and Budget 
(OMB) for each collection of information they conduct or sponsor. 
``Collection of information'' is defined in 44 U.S.C. 3502(3) and 5 CFR 
1320.3(c) and includes agency requests or requirements that members of 
the public submit reports, keep records, or provide information to a 
third party. Section 3506(c)(2)(A) of the PRA (44 U.S.C. 3506(c)(2)(A)) 
requires Federal agencies to provide a 60-day notice in the Federal 
Register concerning each proposed collection of information, including 
each proposed extension of an existing collection of information, 
before submitting the collection to OMB for approval. To comply with 
this requirement, FDA is publishing notice of the proposed collection 
of information set forth in this document.
    With respect to the following collection of information, FDA 
invites comments on these topics: (1) Whether the proposed collection 
of information is necessary for the proper performance of FDA's 
functions, including whether the information will have practical 
utility; (2) the accuracy of FDA's estimate of the burden of the 
proposed collection of information, including the validity of the 
methodology and assumptions used; (3) ways to enhance the quality, 
utility, and clarity of the information to be collected; and (4) ways 
to minimize the burden of the collection of information on respondents, 
including through the use of automated collection techniques, when 
appropriate, and other forms of information technology.

Requirements on Content and Format of Labeling for Human Prescription 
Drug and Biological Products (OMB Control Number 0910-0572)--Extension

    FDA's final rule entitled ``Requirements on Content and Format of 
Labeling for Human Prescription Drug and Biological Products'' (the 
final rule), which published on January 24, 2006 (71 FR 3922), and was 
effective on June 30, 2006, amended FDA's regulations governing the 
format and content of labeling for human prescription drug and 
biological products to require that the labeling of new and recently 
approved products contain highlights of prescribing information, a 
table of contents for prescribing information, reordering of certain 
sections, minor content changes, and minimum graphical requirements. 
These revisions were intended to make it easier for health care 
practitioners to access, read, and use information in prescription drug 
labeling; to enhance the safe and effective use of prescription drug 
products; and to reduce the number of adverse reactions resulting from 
medication errors due to misunderstood or incorrectly applied drug 
information.

A. Summary of Prescription Drug Labeling Content and Format 
Requirements That Contain Collections of Information

    Section 201.56 (21 CFR 201.56) requires that prescription drug 
labeling contain certain information in the format specified in either 
Sec.  201.57 (21 CFR 201.57) or Sec.  201.80 (21 CFR 201.80), depending 
on when the drug was approved for marketing.
    Section 201.56(a) sets forth general labeling requirements 
applicable to all prescription drugs. Section 201.56(b) specifies the 
categories of new and more recently approved prescription drugs subject 
to the revised content and format requirements in Sec. Sec.  201.56(d) 
and 201.57. Section 201.56(c) sets forth the schedule for implementing 
these revised content and format requirements. Section 201.56(e) 
specifies the sections and subsections, required and optional, for the 
labeling of older prescription drugs not subject to the revised format 
and content requirements.
    Section 201.57(a) requires that prescription drug labeling for new 
and more recently approved prescription drug products include 
``Highlights of Prescribing Information.'' Highlights provides a 
concise extract of the most important information required under Sec.  
201.57(c) (the Full Prescribing Information (FPI)), as well as certain 
additional information important to prescribers. Section 201.57(b) 
requires a table of contents to prescribing information, entitled 
``Full Prescribing Information: Contents,'' consisting of a list of 
each heading and subheading along with its identifying number to 
facilitate health care practitioners' use of labeling information. 
Section 201.57(c) specifies the contents of the FPI. Section 201.57(d) 
mandates the minimum specifications for the format of prescription drug 
labeling and establishes minimum requirements for key graphic elements 
such as bold type, bullet points, type size, and spacing.
    Older drugs not subject to the revised labeling content and format 
requirements in Sec.  201.57 remain subject to labeling requirements at 
Sec.  201.80 (in the final rule, former Sec.  201.57 was redesignated 
as Sec.  201.80). Section 201.80(f)(2) requires that within 1 year, any 
FDA-approved patient labeling be referenced in the ``Precautions'' 
section of the labeling of older products and either accompany or be 
reprinted immediately following the labeling.

B. Estimates of Reporting Burden

    The PRA information collection analysis in the final rule (71 FR 
3964 through 3967) (currently approved under OMB Control Number 0910-
0572) estimated the reporting burden for a multi-year period. We are 
requesting that OMB extend approval for the information in this 
collection as described below, which will continue to be submitted to 
FDA during this multi-year period.

Annual Burden for Prescription Drug Labeling Design, Testing, and 
Submitting to FDA for New Drug Applications (NDAs) and Biologics 
License Applications (BLAs) (Sec. Sec.  201.56 and 201.57) (Table 1)

    New drug product applicants must: (1) Design and create 
prescription drug labeling containing Highlights, Contents, and FPI, 
(2) test the designed labeling (e.g., to ensure that the designed 
labeling fits into carton-enclosed products), and (3) submit it to FDA 
for approval. Based on the projected data estimated in the final rule, 
FDA estimates that it takes applicants approximately 3,349 hours to 
design, test, and submit prescription drug labeling to FDA as part of 
an NDA or BLA under the revised regulations. Approximately 85 
applicants submit approximately 107 new applications (NDAs and BLAs) to 
FDA per year, totaling 358,343 hours.

[[Page 56594]]

Burden Associated with Labeling Supplements for Applications Approved 
Within 5 Years Prior to the Effective Date of the Rule (Sec.  201.57) 
(Table 2)

    The final rule required that prescription drug applications 
approved during the 5 years before, or pending on, the effective date 
conform to format and content requirements at Sec.  201.57. For these 
products, applicants must redesign and negotiate the labeling, 
including Highlights and Contents, test the redesigned labeling, and 
prepare and submit that labeling to FDA for approval. Based on the 
projected data estimated in the final rule, labeling supplements for a 
total of approximately 344 innovator products are expected to be 
submitted to FDA over a 5-year period (beginning in year 3 and ending 
in year 7 after the effective date of the final rule). Approximately 
172 applicants submit these labeling supplements, and the time required 
for redesigning, testing, and submitting the labeling to FDA is 
approximately 196 hours per application, totaling 67,424 hours.

Burden Associated with Revised Labeling Efficacy Supplements Submitted 
on or After the Effective Date of the Rule (Sec. Sec.  201.56(d) and 
201.57) (Table 2)

    Efficacy supplemental applications for older drugs submitted to FDA 
on or after the effective date of the final rule are subject to the 
content and format requirements of Sec. Sec.  201.56(d) and 201.57. To 
meet these requirements, applicants must revise the existing labeling 
for these products. Each year an increasing number of innovator drug 
labeling will have been revised, and over time, very few efficacy 
supplements independently will generate labeling revisions. Based on 
the projected data estimated in the final rule, the number of affected 
efficacy supplements over 10 years, beginning with year 3, is 186, with 
a decreasing number each year over the period. Approximately 172 
applicants will trigger approximately 186 efficacy supplements, each 
one requiring approximately 196 hours to revise the labeling in the 
application, totaling 36,456 hours. (As stated in the final rule, in 
addition to this burden, a minimal annual reporting burden (fewer than 
7) will continue indefinitely).

Burden Associated with Revised Labeling for Efficacy Supplements for 
Generic Drug Products (Sec.  201.57) (Table 2)

    Based on the projected data estimated in the final rule, beginning 
in year 3 and continuing throughout the 10-year period analyzed, 
approximately 42 generic applicants per year must submit labeling 
supplements. Approximately 336 already approved generic drug 
applications must submit labeling supplements over the 10-year period 
after the effective date of the rule. The time required to revise and 
submit this labeling to FDA is approximately 27 hours per application, 
totaling 9,072 hours. (As stated in the final rule, in addition to this 
burden, a minimal annual reporting burden associated with a very small 
number of generic applications referencing older drugs may continue 
indefinitely).

C. Capital Costs

    As discussed in the final rule, a small number of carton-enclosed 
products may require new packaging to accommodate longer inserts. As 
many as 5 percent of the existing products affected by the final rule 
(i.e., products with new efficacy supplements, products approved in the 
5 years prior to the effective date of the rule, and affected 
abbreviated new drug applications) may require equipment changes at an 
estimated cost of $200,000 each product.

                                            Table 1.--Estimated Reporting Burden For New Drug Applications\1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                              No. of       No. of Responses per                         Hours per
               Category (21 CFR Section)                   Respondents          Respondent        Total Responses        Response         Total Hours
--------------------------------------------------------------------------------------------------------------------------------------------------------
Annual Burden for Labeling Requirements in Sec.  Sec.                  85                  1.26                107              3,349            358,343
  201.56 and 201.57
--------------------------------------------------------------------------------------------------------------------------------------------------------
Total                                                                                                                                            358,343
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.


        Table 2.--Estimated Reporting Burdens For Labeling Revisions To Already-Approved Drug Products\1\
----------------------------------------------------------------------------------------------------------------
                    Year(s) In
Category (21 CFR  Which Burdens     No. of        No. of         Total      Hours per                   Total
    Section)       Occur After   Respondents   Responses per   Responses     Response   Total Hours    Capital
                  June 30, 2006                 Respondent                                              Costs
----------------------------------------------------------------------------------------------------------------
 Burden           Beginning              172               2          344          196       67,424         $3.3
 associated with   year 3,                                                                               million
 revised           ending year
 labeling for      7
 applications
 approved within
 5 years prior
 to June 30,
 2006 (Sec.
 201.57)
----------------------------------------------------------------------------------------------------------------
Burden            Beginning              172            1.08          186          196       36,456         $2.5
 associated with   year 3,                                                                               million
 revised           diminishing
 labeling for      over time
 efficacy
 supplements
 submitted on or
 after June 30,
 2006 (Sec.
 Sec.
 201.56(d) and
 201.57)
----------------------------------------------------------------------------------------------------------------

[[Page 56595]]


Burden            Beginning               42               8     336 (for           27        9,072         $2.5
 associated with   year 3,                                    years 1-10)                                million
 revised           continuing
 labeling for      annually
 efficacy          thereafter
 supplements for
 generic drug
 products (Sec.
  201.57)
----------------------------------------------------------------------------------------------------------------
Total                                                                                       112,952   Up to $8.3
                                                                                                         million
----------------------------------------------------------------------------------------------------------------
\1\ There are no operating and maintenance costs associated with this collection of information.

    Please note that on January 15, 2008, the FDA Division of Dockets 
Management Web site transitioned to the Federal Dockets Management 
System (FDMS). FDMS is a Government-wide, electronic docket management 
system. Electronic comments or submissions will be accepted by FDA only 
through FDMS at http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.regulations.gov.

    Dated: September 17, 2008.
Jeffrey Shuren,
Associate Commissioner for Policy and Planning.
[FR Doc. E8-22731 Filed 9-26-08; 8:45 am]

BILLING CODE 4160-01-S