[Federal Register Volume 79, Number 88 (Wednesday, May 7, 2014)]
[Notices]
[Pages 26252-26255]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2014-10414]


-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2014-N-0539]


Agency Information Collection Activities; Proposed Collection; 
Comment Request; Prescription Drug Labeling Improvement and Enhancement 
Initiative

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 and 
to allow 60 days for public comment in response to the notice. This 
notice solicits comments on information collection for the Prescription 
Drug Labeling Improvement and Enhancement Initiative (the initiative); 
specifically, information collection associated with the use of 
Government contractor-assisted labeling conversion resources and 
services for certain older drug and biological products (approved 
before June 30, 2001). The intent of the initiative is to enhance the 
safe and effective use of prescription drugs by facilitating optimal 
communication through labeling.

[[Page 26253]]


DATES: Submit either electronic or written comments on the collection 
of information by July 7, 2014.

ADDRESSES: Submit electronic comments on the collection of information 
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: FDA PRA Staff, Office of Operations, 
Food and Drug Administration, 1350 Piccard Dr., PI50-400B, Rockville, 
MD 20850, [email protected].

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 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.

Prescription Drug Labeling Improvement and Enhancement Initiative--(OMB 
Control Number 0910--NEW)

    In the Federal Register of January 24, 2006 (71 FR 3922), FDA 
published the final rule ``Requirements on Content and Format of 
Labeling for Human Prescription Drug and Biological Products,'' which 
revised the content and format requirements to make labeling easier to 
access, read, and use. This final rule is commonly referred to as the 
physician labeling rule (PLR) because it addresses prescription drug 
labeling used by prescribers, including physicians and other health 
care practitioners.\1\
---------------------------------------------------------------------------

    \1\ In this Federal Register document, the term ``PLR format'' 
refers to labeling that meets the content and format requirements in 
Sec. Sec.  201.56(d) and 201.57 (21 CFR 201.56(d) and 201.57).
---------------------------------------------------------------------------

    The PLR applies to products for which a new drug application (NDA), 
biologics license application (BLA), or efficacy supplement (ES) to an 
NDA or BLA was approved between June 30, 2001, and June 30, 2006; was 
pending on June 30, 2006; or was submitted after June 30, 2006. Older 
drug and biological products (approved before June 30, 2001) are not 
subject to the mandatory PLR conversion requirements, but the NDA or 
BLA holder may voluntarily convert the labeling to PLR format. If 
application holders have not voluntarily converted labeling to PLR 
format, labeling for older drug and biological products must be in 
compliance with the requirements under 21 CFR 201.56(e) and 201.80.
    The PLR established a staggered implementation schedule under which 
cohorts of drugs, from newest to oldest, would be converted to the PLR 
labeling format over time.\2\ The staggered implementation for 
conversion to PLR format expired on June 30, 2013.\3\ As of November 
2013, approximately 15 percent of all prescription drugs and biological 
products have labeling in the PLR format.\4\ If no further action is 
taken, the only additional drug products with labeling in the PLR 
format will be new NDAs, BLAs, and ESs, which are required to be 
submitted in PLR format, and labeling for older drug products for which 
the NDA or BLA holder voluntarily converts to PLR format.
---------------------------------------------------------------------------

    \2\ See Sec.  201.56(c). The Agency adopted this approach 
because research conducted during the PLR's development indicated 
that this was the ``most reasonable approach to maximizing the 
public health benefit and best utilizing available resources.'' See 
71 FR 3922 at 3962, January 24, 2006.
    \3\ For the last cohort of drugs approved from June 30, 2001, to 
June 29, 2002, applicants were required to submit PLR conversion 
supplements to FDA by June 30, 2013.
    \4\ Data obtained from http://labels.fda.gov.
---------------------------------------------------------------------------

    To address this issue, FDA proposed the Prescription Drug Labeling 
Improvement and Enhancement Initiative in the Federal Register of 
February 6, 2013 (78 FR 8446), and solicited public comments. 
Specifically, FDA sought feedback on various issues related to the 
feasibility and implementation of the initiative, including the 
following:
     Approaches for identifying and prioritizing drugs and/or 
drug classes for voluntary PLR conversions;
     approaches that application holders would find helpful in 
facilitating voluntary PLR conversions for the specified drugs or drug 
classes;
     approaches for harmonizing labeling for generic drugs for 
which approval of the NDA for the reference listed drug (RLD) has been 
withdrawn;
     use of a Government contractor to provide PLR conversion 
resources and services; and
     overall interest in participating in the initiative.
    In general, public comments posted to the docket (Docket No. FDA-
2013-N-0059) supported the initiative, including the use of a 
Government contractor to ease the resource burden on application 
holders and to facilitate conversion to the PLR format. Some comments 
stated that having FDA (through a Government contractor) facilitate 
conversion of labeling to PLR format for the application holder may: 
(1) Allow for greater clarity and a better understanding of FDA's 
expectations, (2) result in a more efficient review process, and (3) 
expedite the availability of labeling in the PLR format. Thus, as part 
of the initiative, FDA intends to provide PLR conversion resources and 
services, including preparation of draft PLR format labeling, through 
the use of a Government contractor. For this part of the initiative, in 
a phased approach over 5 years, FDA proposes to identify and prioritize 
for PLR conversion approximately 750 prescription drug products not 
subject to the mandatory requirements under Sec. Sec.  201.56(d) and 
201.57 based on criteria that would maximize the benefit to the public 
health, including volume of prescriptions, clinical relevance, and 
risk-based considerations. This part of the initiative includes the 
following two collections of information: (1) The application holder's 
submission of its proposed PLR format labeling to FDA in a supplement 
to its application for products identified by FDA for the initiative 
and (2) the abbreviated new drug application (ANDA) holder's submission 
of a labeling supplement to

[[Page 26254]]

FDA with conforming revisions for generic drug products affected by 
FDA's approval of a labeling change for the corresponding RLD.

Submitting a Supplement to FDA for the Proposed PLR Format Labeling

    FDA will identify labeling to be converted to PLR based on the 
criteria established and, as recommended in comments submitted to the 
public docket, FDA will send an inquiry letter to the respective 
application holders to request their voluntary participation in this 
part of the initiative. The request will include information about the 
initiative, the labeling identified for PLR conversion, and a request 
for participation. FDA intends to provide Government contractor-
assisted PLR conversion resources and services to application holders 
who participate. FDA will review the draft PLR format labeling prepared 
by the contractor for content and format, and send a draft version to 
the application holder for review. FDA will request that the 
application holder review the draft labeling and submit a supplement to 
its application to FDA with its proposed PLR format labeling, which may 
include proposed revisions to the draft labeling. It should be 
emphasized that the application holder always bears responsibility for 
the content of its product labeling, and FDA's provision of contract 
resources is intended to facilitate conversion to the PLR format.

Submitting a Labeling Supplement to FDA for Generic Drug Products 
Affected by the RLD Labeling Change

    After FDA approves a supplement to an NDA as a result of this part 
of the initiative, ANDA holders that relied on the NDA as their RLD 
will be required to revise the generic drug product labeling so that it 
conforms to the approved PLR-converted labeling of the RLD (see 21 CFR 
314.94(a)(8)(iv) and 314.150(b)(10)). The guidance for industry 
entitled ``Revising ANDA Labeling Following Revision of the RLD 
Labeling'' provides information to ANDA holders on how to submit 
conforming labeling changes as a Special Supplement--Changes Being 
Effected.\5\
---------------------------------------------------------------------------

    \5\ This guidance is available on the Internet at http://www.fda.gov//Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm under Guidances (Drugs).
---------------------------------------------------------------------------

    Description of Respondents: The respondents to this collection of 
information are persons and businesses, including small businesses and 
manufacturers.
    Burden Estimates: FDA currently has OMB approval for the submission 
of labeling supplements under 21 CFR 314.70 and 314.97 (OMB control 
number 0910-0001) and approval for the design, testing, and production 
of prescription drug labeling under Sec. Sec.  201.56 and 201.57 (OMB 
control number 0910-0572). This notice provides burden estimates 
associated with submitting additional labeling supplements as a result 
of this initiative.
    Table 1 of this document provides an estimate of the reporting 
burden for: (1) Submitting a supplement to FDA for the proposed PLR 
format labeling and (2) submitting a labeling supplement to FDA for 
generic drug products affected by an FDA-approved change to the RLD 
labeling. In table 1, the estimated averages for the number of 
respondents and the hours per response were obtained using the 
collections of information described in the PLR (71 FR 3922, January 
24, 2006).

Submitting a Supplement to FDA for the Proposed PLR Format

    Based on the labeling conversion of approximately 750 prescription 
drug products not subject to the mandatory requirements under 
Sec. Sec.  201.56 and 201.57, we estimate that 375 application holders 
will be contacted for voluntary participation in this part of the 
initiative, which is intended to occur in a phased approach over 5 
years. Some application holders may receive more than one request to 
participate based on the process to identify and prioritize labeling.
    The hours per response is the estimated number of hours an 
application holder would spend reviewing and responding to the request 
to participate, reviewing the draft PLR format labeling, modifying the 
labeling as appropriate, and submitting a supplement to FDA. We 
estimate that approximately 196 hours on average would be needed per 
submission, totaling 147,000 hours (see row 1 of table 1).

Submitting a Labeling Supplement to FDA for Generic Drug Products 
Affected by the RLD Labeling Change

    FDA estimates that 1,864 generic drug products \6\ will require 
labeling supplements from approximately 233 application holders, based 
on approved PLR-converted RLD labeling from this part of the 
initiative. The hours per response is the estimated number of hours a 
generic drug application holder would spend revising the ANDA labeling 
so that it conforms to the PLR-converted RLD labeling and submitting a 
labeling supplement to FDA. We estimate that approximately 27 hours on 
average would be needed per submission, totaling 50,328 hours (see row 
2 of table 1).
---------------------------------------------------------------------------

    \6\ Estimate based on the ratio of ANDA to NDA labeling in 
http://labels.fda.gov.
---------------------------------------------------------------------------

Capital Costs

    In 2006, the PLR described that a small number of carton-enclosed 
products may require new packaging to accommodate longer inserts for 
labeling in PLR format (71 FR 3922 at 3966). The PLR indicates that up 
to 5 percent of existing products affected by the rule may require 
equipment changes at an estimated cost of $200,000 for each product. 
Because the PLR has been in effect since 2006, we estimate that 
equipment changes may only be required for up to 1 percent of existing 
products that may be involved with this initiative. Therefore, we 
estimate that approximately 26 existing products could incur capital 
costs as a result of participating in the initiative, at a current cost 
of $245,400 per product. The estimated cost of changes to equipment 
totals $6.4 million.
    In 2006, the PLR also estimated $8,700 as the average cost to a 
firm to: (1) Redesign the labeling of an existing drug (e.g., drug-
specific decisions regarding exactly which adverse reactions should be 
listed in the highlights section), (2) test the redesigned labeling 
(e.g., to ensure that the larger labeling will still fit in carton-
enclosed products), and (3) prepare and submit the labeling to FDA for 
approval. The PLR estimated $6,190 as the average cost to design 
labeling for new applications and efficacy supplements (71 FR 3922 at 
3978). Thus, the 2006 estimated average cost to test the redesigned 
labeling and to prepare and submit the labeling to FDA for approval is 
calculated as $2,510 ($8,700 minus $6,190). For this part of the 
initiative, the Government contractor will provide a draft redesign of 
the labeling for application holders. Therefore, we estimate that 
approximately 608 application holders could incur capital costs as a 
result of participating in the initiative, at a current cost of $2,952 
per product. The estimated cost of testing, preparing, and submitting 
the labeling to FDA for approval totals $7.7 million.

Operating and Maintenance Costs

    In 2006, the PLR described that manufacturers may incur incremental 
printing costs because the content and format requirements of the final 
rule will lengthen labeling (71 FR 3922 at 3979). The PLR estimated 
that the annual per-product cost for innovator and generic products was 
$1,165 and $700, respectively. For this initiative,

[[Page 26255]]

we estimate the current annual per-product cost for innovator and 
generic products as $1,429 and $859, respectively. Therefore, we 
estimate that the total incremental printing costs for innovator and 
generic products are approximately $1.1 million and $1.6 million, 
respectively, over the 5-year period of the program.
    FDA estimates the burden of this collection of information as 
follows:

                                               Table 1--Estimated Reporting Burden Over a 5-Year Period 1
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                               Total
                                                             Number of                    Average burden                   Total capital   operating and
 Prescription drug labeling improvement      Number of     responses per       Total       per response     Total hours        costs        maintenance
       and enhancement initiative           respondents     respondent       responses        (hours)                       ($million)         costs
                                                                                                                                            ($million)
--------------------------------------------------------------------------------------------------------------------------------------------------------
Submitting a supplement to FDA for the               375               2             750             196         147,000            $4.0            $1.1
 proposed PLR format labeling...........
Submitting a labeling supplement to FDA              233               8           1,864              27          50,328            10.1             1.6
 for generic drug products affected by
 the RLD labeling change................
                                         ---------------------------------------------------------------------------------------------------------------
    Total...............................  ..............  ..............  ..............  ..............         197,328            14.1             2.7
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ Numbers may not sum due to rounding.


    Dated: May 1, 2014.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2014-10414 Filed 5-6-14; 8:45 am]
BILLING CODE 4160-01-P