[Federal Register Volume 78, Number 10 (Tuesday, January 15, 2013)]
[Notices]
[Pages 3005-3008]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2013-00607]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2012-N-1248]


Creating an Alternative Approval Pathway for Certain Drugs 
Intended to Address Unmet Medical Need; Public Hearing; Request for 
Comments

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of public hearing; request for comments.

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SUMMARY: The Food and Drug Administration (FDA) is announcing a public 
hearing to obtain input on a potential new pathway to expedite the 
development of drugs, including biological products, for serious or 
life-threatening conditions that would address an unmet medical need. 
The drug's safety and effectiveness would be studied in a smaller 
subpopulation of patients with more serious manifestations of a 
condition. Such a pathway could involve smaller and more rapid clinical 
trials than would occur if the drug were studied in a broader group of 
patients with a wide range of clinical manifestations. The labeling of 
drugs approved using this pathway would make clear that the drug is 
narrowly indicated for use in limited, well-defined subpopulations in 
which the drug's benefits have been shown to outweigh its risks. The 
purpose of the public hearing is to obtain information and comments 
from the public on the need for and feasibility of this pathway and its 
potential advantages and disadvantages.

DATES: Dates and Time: The public hearing will be held on February 4 
and 5, 2013, from 9 a.m. to 4 p.m. The public hearing may be extended 
or may end early depending on the level of public participation.
    Attendance, Presentations, and Comments: Individuals who wish to 
attend or present at the public hearing must register on or before 5 
p.m. e.s.t. on January 22, 2013. To register for the

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public hearing, email your registration information to 
[email protected]. Section IV of this document 
provides attendance and registration information. Either electronic or 
written comments will be accepted after the hearing until March 1, 
2013.

ADDRESSES: The public hearing will be held at FDA's White Oak Campus, 
10903 New Hampshire Ave., Building 31 Conference Center, the Great Room 
(Rm. 1503), Silver Spring, MD, 20993-0002. Entrance for the public 
meeting participants (non-FDA employees) is through Building 1 where 
routine security check procedures will be performed. For parking and 
security information, please refer to http://www.fda.gov/AboutFDA/WorkingatFDA/BuildingsandFacilities/WhiteOakCampusInformation/ucm241740.htm.
    Submit electronic comments to http://www.regulations.gov. Submit 
written comments to the Division of Dockets Management (HFA-305), Food 
and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 
20852.

FOR FURTHER INFORMATION CONTACT:
Jonas Santiago, Center for Drug Evaluation and Research, Food and Drug 
Administration, 10903 New Hampshire Ave., Silver Spring, MD 20993-0002, 
301-796-5346, Fax: 301-847-3529, email: 
[email protected];

or

Stephen Ripley, Center for Biologics Evaluation and Research (HFM-17), 
Food and Drug Administration, 1401 Rockville Pike, Suite 200N, 
Rockville, MD 20852-1448, 301-827-6210.

SUPPLEMENTARY INFORMATION: FDA is announcing a public hearing to obtain 
input on a potential new pathway for approving drugs, including 
biological products, targeted at serious or life-threatening conditions 
and intended to address an unmet medical need. The drug's safety and 
effectiveness would be studied in a smaller subpopulation of patients 
with more serious manifestations of a condition. Such a pathway could 
involve smaller and more rapid clinical trials than would occur if the 
drug were studied in a broader group of patients with a wide range of 
clinical manifestations. The labeling of drugs approved using this 
pathway would make clear that the drug is narrowly indicated for use in 
limited, well-defined subpopulations in which the drug's benefits have 
been shown to outweigh the risks.

I. Background

    In the last two decades, major advances in molecular and cellular 
biology have greatly expanded our understanding of a broad range of 
complex disease processes and have led to major advances in the 
treatment of conditions such as cystic fibrosis, HIV, hepatitis C, and 
multiple sclerosis. In some cases, however, the resource-intensive 
programs needed for approval of drugs to treat a broad condition with a 
wide range of clinical manifestations require very large study 
populations and can hinder the ability to make promising new drugs 
available in a timely manner to subpopulations of patients with 
important unmet medical needs. FDA recognizes its role in fostering the 
application of scientific advances to the treatment of disease through 
drug development, including the use of novel approaches that can 
facilitate development of treatment for unmet needs.
    Traditional drug development programs are designed to evaluate the 
benefits and risks of treatment with a high degree of precision for the 
range of manifestations of a disease or condition. Often this will 
involve studies that expose a large number of patients to the drug, 
normally for an extended period of time. In some cases, such as when 
safety issues have arisen with prior drugs in a class, additional 
trials are needed to help identify serious but infrequent risks. 
Typically, these studies are needed when there is an expectation that 
the drug will be used broadly in patients with less severe 
manifestations of the condition.
    Existing processes to expedite drug development and review of 
important new therapies have worked effectively in many circumstances. 
For example, more than 100 new therapies and indications have been 
approved under the accelerated approval process (21 CFR part 314, 
subpart H; 21 CFR part 601, subpart E).\1\ In addition, FDA's existing 
flexibility in applying the statutory requirements for approval has 
effectively facilitated development of drugs for conditions where the 
entire intended patient population has serious unmet medical needs. 
However, FDA believes that it is important to explore the need for and 
feasibility of a new process focused on developing drugs for 
subpopulations of patients with serious or life-threatening conditions, 
including patients with serious or life-threatening infections caused 
by antibiotic-resistant bacteria.
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    \1\ See a list of Center for Drug Evaluation and Research Drug 
and Biologic Accelerated Approvals as of September 30, 2011, 
available at http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/DrugandBiologicApprovalReports/UCM278506.pdf.
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II. New Pathway

    FDA is seeking input on a potential new pathway to approve drugs 
for use in limited, well-defined subpopulations of patients with 
serious or life-threatening conditions for whom the benefits of the 
drug have been shown to outweigh the risks. The pathway could include 
product labeling with a specific designation to make clear that the 
drug indication is limited to the narrow subpopulation and the 
rationale for limiting use to that population. The pathway also might 
provide for the designation and an appropriate logo to appear on a 
drug's container label.
    This designation could be designed to inform the health care 
community, including practitioners, payers, and patients, of compelling 
reasons to carefully manage use of such drugs, limiting use to 
appropriate patients, as the benefit-risk profile only warrants use in 
the identified subpopulation. In addition, the potential new pathway 
could be used to help reduce the development of resistance to important 
antibacterial drugs by limiting their use to those patients in whom use 
is appropriate and necessary.
    This approval of a narrow indication could be broadened if 
additional data become available which demonstrate the safety and 
effectiveness of the drug in treating a broader condition or patient 
population. For example, a drug could be initially approved using this 
pathway for a narrow subpopulation of patients because of uncertainty 
about a cardiovascular risk that would not be acceptable in a broad 
population. If a long-term study subsequently demonstrates that the 
benefit-risk profile makes the drug appropriate for broader use, the 
designation could be removed. Alternatively, there may be drugs for 
which we would not anticipate the possibility of approval in the 
broader population, such as when there is a known toxicity that, while 
acceptable in patients with serious manifestations of a condition, 
would not be appropriate for use in patients with milder manifestations 
of the condition.
    The proposed pathway was recommended by the President's Council of 
Advisors on Science and Technology (PCAST) in their September 2012 
``Report to the President on Propelling Innovation in Drug Discovery, 
Development, and Evaluation,'' as a way to improve drug evaluation. The 
PCAST recommendations support the goal of increasing the output of 
innovative, new medicines for patients with important unmet medical 
needs, while increasing drug efficacy and safety, through

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industry, academia, and government working together to decrease 
clinical failure, clinical trial costs, time to market, and regulatory 
uncertainty.\2\
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    \2\ For more information on the PCAST Report to the President on 
Propelling Innovation in Drug Discovery, Development, and 
Evaluation, see http://www.whitehouse.gov/sites/default/files/microsites/ostp/pcast-fda-final.pdf.
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III. Scope of the Public Hearing and Discussion Questions

    FDA is holding this public hearing to seek input from interested 
members of the public including patients and consumers, practitioners 
and other members of the medical community, regulated industry, 
insurers, and managed care organizations on a potential new pathway to 
approve drugs shown to be safe and effective in a subpopulation of 
patients with serious or life-threatening conditions in which an unmet 
medical need exists. FDA is interested in obtaining information and 
public comment on the following issues:
    1. Considering existing processes to expedite drug development and 
review of important new therapies (i.e., accelerated approval, fast-
track designation), would this new pathway increase the therapeutic 
options for serious or life-threatening conditions for which an unmet 
medical need exists? If not, what might be some alternative approaches?
    2. Can you identify specific serious or life-threatening conditions 
for which an unmet medical need exists and for which this approval 
pathway may benefit subpopulations of patients?
    3. What approaches could be undertaken (by FDA or by people or 
organizations other than FDA) to monitor use of drugs approved under 
this pathway to determine whether they are being used inconsistent with 
the terms of approval? What approaches could be undertaken to prevent, 
manage, or monitor use in a broader population where safety and 
efficacy has not been demonstrated? For example, if this pathway were 
adopted to approve new antibacterial drugs when limited use was needed 
(e.g., to prevent the emergence of further antimicrobial resistance), 
what other measures (by FDA or by people or organizations other than 
FDA) might ensure that these products are used appropriately only in 
the indicated subpopulations?
    4. Would this pathway help to address some of the current 
challenges in antibacterial drug development, particularly for serious 
or life-threatening infections for which there is an unmet medical 
need?
    5. This potential pathway could be used to approve drugs for a 
limited subpopulation based upon smaller clinical trials, when benefit-
risk is appropriate for the limited population but safety and efficacy 
have not been demonstrated for use in a broader population of patients 
or patients with less severe manifestations of the condition. For the 
serious or life-threatening conditions you identified in question 2, 
what benefit-risk considerations need to be taken into account before 
and after marketing and how should they be addressed?
    6. Would the use of a formal designation and logo to reflect 
approval under this pathway, with clear labeling of clinical 
information that only supports use in the indicated subpopulation, but 
without other constraints from FDA be effective in limiting use to the 
indicated subpopulation? Why or why not?

IV. Attendance, Registration, and Requests for Oral Presentations

    The public hearing is free and seating will be on a first-come, 
first-served basis. Attendees, including those not presenting, need to 
register for the public hearing.
    If you wish to attend or make an oral presentation during the 
hearing, you must register by submitting either an electronic or 
written request received on or before January 22, 2013. (See FOR 
FURTHER INFORMATION CONTACT.) You must provide your name, title, 
business affiliation (if applicable), address, telephone and fax 
numbers, email address, and type of organization you represent (e.g., 
industry, consumer organization). If requesting to present, you also 
should submit a brief summary of the presentation, including the 
discussion question(s) that will be addressed and the approximate time 
requested for your presentation. FDA has included discussion questions 
in section III of this document. You should identify the question(s) 
and the number of each question you wish to address in your 
presentation. We encourage individuals and organizations with common 
interests to consolidate or coordinate their presentations to allow 
adequate time for each request for presentation. FDA will do its best 
to accommodate requests to speak and will determine the amount of time 
allotted for each oral presentation, and the approximate time that each 
oral presentation is scheduled to begin. Persons registered to make an 
oral presentation should submit to FDA an electronic copy of their 
presentation and an abstract to [email protected] 
on or before January 30, 2013.
    If you need special accommodations because of a disability, please 
contact Jonas Santiago (see FOR FURTHER INFORMATION CONTACT) at least 7 
days before the meeting.

V. Notice of Hearing Under 21 CFR Part 15

    The Commissioner of Food and Drugs is announcing that the public 
hearing will be held in accordance with part 15 (21 CFR part 15). The 
hearing will be conducted by a presiding officer, who will be 
accompanied by FDA senior management.
    Under Sec.  15.30(f), the hearing is informal and the rules of 
evidence do not apply. No participant may interrupt the presentation of 
another participant. Only the presiding officer and panel members may 
question any person during or at the conclusion of each presentation.
    Public hearings under part 15 are subject to FDA's policy and 
procedures for electronic media coverage of FDA's public administrative 
proceedings (part 10 (21 CFR part 10, subpart C)). Under Sec.  10.205, 
representatives of the electronic media may be permitted, subject to 
certain limitations, to videotape, film, or otherwise record FDA's 
public administrative proceedings, including presentations by 
participants. The hearing will be transcribed as stipulated in Sec.  
15.30(b) (see section VII of this document).
    To the extent that the conditions for the hearing, as described in 
this notice, conflict with any provisions set out in part 15, this 
notice acts as a waiver of those provisions as specified in Sec.  
15.30(h).

VI. Comments

    Interested persons may submit either electronic comments to http://www.regulations.gov or written comments regarding this document to the 
Division of Dockets Management (see ADDRESSES). It is only necessary to 
send one set of comments. Identify comments with the docket number 
found in brackets in the heading of this document. In addition, when 
responding to specific questions as discussed in section III of this 
document, please identify the question you are addressing. Received 
comments 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.

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VII. Transcripts

    Transcripts of the public hearing will be available for review at 
the Division of Dockets Management (see ADDRESSES) and on the Internet 
at http://www.regulations.gov approximately 30 days after the public 
hearing. A transcript will also be made available in either hard copy 
or on CD-ROM, upon submission of a Freedom of Information request. 
Written requests are to be sent to the Division of Freedom of 
Information (ELEM-1029), Food and Drug Administration, 12420 Parklawn 
Dr., Element Bldg., Rockville, MD 20857.

    Dated: January 9, 2013.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2013-00607 Filed 1-14-13; 8:45 am]
BILLING CODE 4160-01-P