[Federal Register Volume 78, Number 25 (Wednesday, February 6, 2013)]
[Proposed Rules]
[Pages 8446-8448]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2013-02528]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 201, 314, and 601

[Docket No. FDA-2013-N-0059]


Center for Drug Evaluation and Research; Prescription Drug 
Labeling Improvement and Enhancement Initiative; Request for Comments 
and Information

AGENCY: Food and Drug Administration, HHS.

ACTION: Notification of an initiative; request for comments and 
information.

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SUMMARY: The Food and Drug Administration (FDA) is announcing the 
establishment of a docket to receive comments on the proposed 
implementation of FDA's Prescription Drug Labeling Improvement and 
Enhancement Initiative and on a proposed pilot project relating to the 
voluntary conversion of labeling to the ``Physician Labeling Rule 
(PLR)'' format described in the 2006 FDA final rule, ``Requirements on 
Content and Format of Labeling for Human Prescription Drug and 
Biological Products.'' The purpose of the initiative and the pilot 
project is to enhance the safe and effective use of prescription drugs 
by facilitating optimal communication through labeling. FDA is seeking 
public comment on this initiative, and the pilot project, particularly 
from stakeholders who develop and use prescription drug labeling. 
Comments received from stakeholders will assist the Agency in 
identifying and addressing feasibility and implementation issues 
associated with this initiative.

[[Page 8447]]


DATES: Submit either electronic or written comments by March 8, 2013.

ADDRESSES: Submit electronic comments to http://www.regulations.gov. 
Submit written comments to the Division of Dockets Management (HFA-
301), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, 
Rockville, MD 20852. Identify comments with the docket number found in 
brackets in the heading of this document.

FOR FURTHER INFORMATION CONTACT: Connie Wisner, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, rm. 6360, Silver Spring, MD 20993-0002, 301-
796-8509, FAX: 301-847-3529, email: connie.wisner@fda.hhs.gov.

SUPPLEMENTARY INFORMATION:

I. Background

    Prescription drug labeling, commonly called the package insert or 
prescribing information, is a compilation of information approved by 
FDA about the safe and effective use of the product, based on FDA's 
thorough analysis of the new drug application (NDA) or biologics 
license application (BLA) submitted by the applicant. Its primary 
purpose is to provide health care practitioners with the essential 
information needed to facilitate prescribing decisions, thereby 
enhancing the safe and effective use of prescription drug products and 
reducing the likelihood of medication errors.
    FDA implemented standardized prescription drug labeling in 1979 (44 
FR 37434, June 26, 1979). However, over the ensuing 25 years, labeling 
became increasingly lengthy and complex, which affected its usefulness 
to healthcare professionals. To address this issue, FDA evaluated the 
usefulness of prescription drug labeling among healthcare professionals 
to determine whether and how its content and format could be improved 
and completed a rulemaking focused on enhanced prescription drug 
labeling.
    In 2006, 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 for 
labeling to make it easier to access, read, and use (71 FR 3922, 
January 24, 2006). The rule is commonly referred to as the ``Physician 
Labeling Rule'' (PLR or final rule) because it addresses prescription 
drug labeling that is used by prescribers, including physicians and 
other healthcare practitioners.\1\
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    \1\ In this Federal Register document, the term ``PLR format'' 
refers to labeling that meets the content and format requirements at 
Sec. Sec.  201.56(d) and 201.57 (21 CFR 201.56(d) and 201.57). The 
term ``old format'' refers to labeling that meets the requirements 
at Sec.  201.56(e) and 21 CFR 201.80.
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    The final rule applies to products for which an NDA, BLA, or 
efficacy supplement (ES) was approved between June 30, 2001, and June 
30, 2006, and to NDAs, BLAs, and ESs submitted after June 30, 2006. The 
rule established a staggered implementation schedule, under which 
cohorts of drugs, from newest to oldest would be converted to the new 
labeling format over time.\2\ The staged implementation for PLR 
conversion expires on June 30, 2013.\3\ Older drugs approved before 
June 30, 2001, are not subject to the mandatory PLR conversion 
requirement, but FDA strongly encourages all applicants to voluntarily 
convert the labeling of their drug products to the PLR format, 
regardless of the date of approval.
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    \2\ See Sec.  201.56(c). The Agency adopted this approach 
because research conducted during the final rule'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\ The last cohort of drugs approved from June 30, 2001, to 
June 29, 2002, must submit PLR conversion supplements to FDA by June 
30, 2013.
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    As of November 2012, 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 ES, which are 
required to be submitted in PLR format, and labeling for drug products 
for which the NDA or BLA holder voluntarily converts to PLR format.
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    \4\ Data obtained from http://labels.fda.gov.
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    Generic drugs approved under an abbreviated new drug application 
(ANDA) are not required to convert their labeling to PLR format unless 
the reference-listed drug (RLD) approved in an NDA has converted to PLR 
format. Recent data show that only 10 percent of generic drug labeling 
has been converted to the PLR format.\5\ Since nearly 80 percent of 
prescriptions today are filled with generic drugs,\6\ FDA believes that 
it is in the best interest of the public health to facilitate 
conversion of generic drug labeling to the PLR format so the labeling 
is equally useful to prescribers as the labeling for more recently 
approved drug products.
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    \5\ Ibid.
    \6\ See http://www.fda.gov/Drugs/ResourcesForYou/Consumers/BuyingUsingMedicineSafely/UnderstandingGenericDrugs/ucm167991.htm.
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    Additional FDA outreach corroborates the usefulness of drug 
labeling in PLR format. On April 20, 2012, the Brookings Institute 
Engelberg Center for Health Care Reform, in cooperation with FDA, held 
an expert meeting \7\ to obtain feedback from healthcare practitioners 
on the utility of the prescription drug labeling as a communication 
tool and to discuss strategies for making it more accessible. In 
general, meeting participants were very supportive of the PLR format 
and in agreement that it improves accessibility and use in electronic 
systems. Moreover, stakeholders, particularly physicians and 
pharmacists, requested that all labeling be available in PLR format, 
including labeling for generic drugs and older drug products outside 
the current PLR implementation schedule.
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    \7\ For more information on the Expert Meeting, see http://www.brookings.edu/events/2012/04/20-expert-workshop-prescribing-info. (FDA has verified the Web site address, but FDA is not 
responsible for any subsequent changes to the Web site after this 
document publishes in the Federal Register.)
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    All holders of marketing applications for drugs and biological 
products have an ongoing obligation to ensure their labeling is 
accurate and up-to-date. For example, when new information comes to 
light that causes information in labeling to become inaccurate, the 
application holder must take steps to change the content of its 
labeling, in accordance with 21 CFR 314.70, 314.97, and 601.12. The PLR 
format represents a more useful and modern approach for communicating 
accurate and up-to-date information on the safe and effective use of 
drugs and makes prescription information more accessible for use with 
electronic prescribing tools and other electronic information 
resources. For these reasons, FDA is proposing to implement the 
Prescription Drug Labeling Improvement and Enhancement Initiative to 
ensure that the safe and effective use of prescription drugs is 
communicated optimally through labeling.

II. Prescription Drug Labeling Improvement and Enhancement Initiative

    The focus of the initiative is to increase the number of drugs with 
labeling that complies with the PLR content and format requirements 
(Sec. Sec.  201.56(d) and 201.57) for drugs approved before June 30, 
2001, and for generic drugs. The initiative is anticipated to take 
place over several years. FDA intends to request that applicants with 
NDAs, BLAs, or ESs approved before June 30, 2001, and generic drugs for 
which the NDA for the RLD has been withdrawn (for reasons

[[Page 8448]]

other than safety or effectiveness) voluntarily convert their labeling 
to PLR format and submit it to FDA for approval.\8\ FDA intends to 
identify and prioritize certain drugs and drug classes based on public 
health impact (e.g., most prescribed, higher risk).
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    \8\ See Sec. Sec.  314.150(a) and (b). An NDA holder that has 
discontinued marketing a drug product, but has not requested 
withdrawal of the NDA, must still comply with applicable statutory 
and regulatory requirements. Such requirements include, for example, 
submission of an annual report (including a brief summary of 
significant new information from the previous year that might affect 
the safety, effectiveness, or labeling of the drug product, and a 
description of actions the applicant has taken or intends to take as 
a result of this new information) and, if appropriate, proposed 
revisions to product labeling.
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    As part of the initiative, FDA is considering, through the use of a 
Government contractor, providing PLR conversion resources and services, 
including preparation of draft PLR labeling for applicants who request 
FDA's assistance to convert labeling to PLR format. For draft labeling 
converted to PLR format by a Government contractor, FDA would review 
the draft labeling prepared by the contractor and then send the 
applicant the proposed draft PLR format labeling. The applicant would 
then submit a labeling supplement to FDA with its proposed PLR format 
labeling (which may include proposed revisions to the draft PLR 
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.
    This initiative differs from the original PLR implementation plan 
in the final rule in that the Agency is not proposing rulemaking at 
this time. Rather, FDA would like to explore a voluntary approach to 
PLR conversions with NDA and BLA holders for drugs approved before June 
30, 2001, and ANDA holders for drugs for which the NDA for the RLD has 
been withdrawn. In light of the public health benefit realized by 
labeling in PLR format, and previous interest by many ANDA holders in 
converting labeling for their drug products to PLR format, FDA 
anticipates that application holders will be interested in 
participating in this voluntary approach to enhance communication of 
information about the drug's safe and effective use through product 
labeling.
    To determine the best approach to accomplish the objectives of this 
initiative, FDA is considering performing a pilot project to identify 
best practices and to standardize the approach for voluntary PLR format 
conversions. FDA is seeking interested applicants with NDAs, BLAs, or 
ESs approved before June 30, 2001, and generic drugs for which the NDA 
for the RLD has been withdrawn to voluntarily participate in this pilot 
project.

III. Establishment of a Docket and Request for Comments and Information

    FDA is soliciting public comments on the Prescription Drug 
Improvement and Enhancement Initiative. FDA is specifically seeking 
feedback on the following:
    1. What specific feasibility issues or other factors should FDA 
consider in its proposed pilot project and implementation of the 
Prescription Drug Labeling Improvement and Enhancement Initiative?
    2. What factors should FDA consider in identifying and prioritizing 
drugs and/or drug classes for voluntary PLR conversions?
    3. What approaches would application holders find helpful in 
facilitating voluntary PLR conversions for the specified drugs or drug 
classes? For example, please comment on the following approaches for 
communicating with applicants:
     Inquiry letter that identifies a drug proposed for PLR 
format conversion and requests information from the application holder 
regarding its preferred approach for possible PLR conversion (i.e., 
application holder or Government contractor)?
     Supplement request letter with draft labeling that has 
been converted to the PLR format attached?
    4. For generic drugs for which the NDA for the RLD has been 
withdrawn, what procedures should FDA use to harmonize feedback from 
multiple ANDA holders on proposed draft labeling in the PLR format?
    5. Would your company be interested in participating in the pilot 
project and the broader Prescription Drug Improvement and Enhancement 
Initiative? Why or why not?
    Suggestions, recommendations, or comments should describe relevant 
considerations that may impact the feasibility or implementation of the 
initiative or the impact the initiative may have on prescription drug 
labeling issues. We also encourage commenters to include 
recommendations on how such prescription drug labeling issues could be 
addressed.
    FDA will consider all suggestions, recommendations, and comments; 
however, the Agency will not respond directly to the person or 
organization making the suggestion, recommendation, or comment.

IV. Comments

    Interested persons may submit either electronic comments 
information regarding this document to http://www.regulations.gov or 
written comments to the Division of Dockets Management (see ADDRESSES). 
It is only necessary to send one set of comments or information. 
Identify comments or information with the docket number found in 
brackets in the heading of this document. Received comments or 
information may be seen in the Division of Dockets Management between 9 
a.m. and 4 p.m., Monday through Friday, and will be posted to the 
docket at http://www.regulations.gov.

    Dated: January 31, 2013.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2013-02528 Filed 2-5-13; 8:45 am]
BILLING CODE 4160-01-P