[Federal Register Volume 72, Number 9 (Tuesday, January 16, 2007)]
[Notices]
[Pages 1743-1753]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 07-122]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. 2007N-0005]
Prescription Drug User Fee Act; Public Meeting
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice of public meeting.
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SUMMARY: The Food and Drug Administration (FDA, we) is publishing
proposed recommendations for the reauthorization of the Prescription
Drug User Fee program for the process of human drug application review
for fiscal years (FY) 2008 to 2012. These proposed recommendations were
developed after discussions with regulated industry and consultation
with appropriate scientific and academic experts, healthcare
professionals, and representatives of patient and consumer advocacy
groups. Section 505 of the Public Health Security and Bioterrorism
Preparedness and Response Act of 2002, enacted June 12, 2002, directs
FDA to publish these proposed recommendations in the Federal Register;
hold a meeting at which the public may present its views on such
recommendations; and provide for a period of 30 days for the public to
provide written comments on such recommendations.
DATES: The public meeting will be held on February 16, 2007, from 9
a.m. to 5 p.m. Submit written comments by February 23, 2007.
Registration to attend the meeting must be received by February 2,
2007.
ADDRESSES: The meeting will be held at the Grand Hyatt Washington at
Washington Center, 1000 H St. NW., Washington, DC 20001. Located at the
Metro Center metro stop. Follow 11th St. exit to the lobby of the Grand
Hyatt. For additional directions, see the hotel Web site at: http://grandwashington.hyatt.com/hyatt/hotels/.
Submit written comments to the Division of Dockets Management (HFA-
305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061,
Rockville, MD 20852. Submit electronic comments to http://www.fda.gov/dockets/ecomments.
FOR FURTHER INFORMATION CONTACT:
For information regarding this document, contact: Ann Sullivan,
Office of Policy and Planning (HFP-20), Food and Drug Administration,
5600 Fishers Lane, Rockville, MD 20857, 301-827-5887, FAX: 301-827-
5225, e-mail: [email protected].
For information regarding registration, contact: Bernadette
Kawaley, Office of Communication, Training and Manufacturers Assistance
(HFM-49), Food and Drug Administration, Center for Biologics Evaluation
and Research, 1401 Rockville Pike, suite 200N, Rockville, MD 20852,
301-827-2000, FAX: 301-827-3079.
SUPPLEMENTARY INFORMATION:
I. Introduction
The Prescription Drug User Fee Act (PDUFA I), first enacted in 1992
(Public Law 102-571, October 29, 1992), authorized FDA to collect user
fees from regulated industry that were to be dedicated to expediting
the review of human drug applications in accordance with certain
performance goals identified in letters from the Secretary of Health
and Human Services to the Chairman of the Energy and Commerce Committee
of the House of Representatives and the Chairman of the Labor and Human
Resources Committee of the Senate (138 Cong. Rec. H9099-H9100 (daily
ed. September 22, 1992)). In 1997, as PDUFA I expired, Congress passed
the Food and Drug Administration Modernization Act (FDAMA, Public Law
105-115). FDAMA included, among other things, an extension of PDUFA
(PDUFA II) for an additional 5 years. In 2002, Congress extended PDUFA
again for 5 years (PDUFA III) through the Public Health
[[Page 1744]]
Security and Bioterrorism Preparedness and Response Act (Public Law
107-188).
Before PDUFA, FDA's review process was more unpredictable, and
slower. At the same time, regulators in other countries were able to
review products faster. Access to new medicines for U.S. patients
lagged behind. For example, a 1989 study by researchers at Tufts
University, analyzing differences in the number of new drugs introduced
and time to marketing in the United Kingdom compared to the United
States for the period 1977 to 1987, found that the United Kingdom led
the United States in the number of first introductions of new drugs
(114 versus 41) and in the average lead time for mutually available
drugs (60.7 months lead time in the United Kingdom versus 28.9 months
in the United States) and in the number of exclusively available new
drugs (70 versus 54).\1\ In addition, a 1992 review of the
international literature related to drug lag found that most studies
reported the United States, Sweden and Norway to have a long delay in
the introduction of new drugs, while the United Kingdom and (West)
Germany were generally found to have the shortest delay.\2\ Chronic
understaffing of drug review and related delays in U.S. patient access
to new drugs led to the 1992 enactment of PDUFA. PDUFA provided FDA
with added funds that enabled the agency to hire additional reviewers
and support staff and upgrade its information technology systems to
speed the application review process for new drugs and biological
products without compromising FDA's high standards for approval.
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\1\ Kaitin, K.I., N. Mattison, F.K. Northington, L. Lasagna, The
drug lag: an update of new drug introductions in the United States
and in the United Kingdom, 1977 through 1987,Clinical Pharmacology
and Therapeutics, 1989; 46 (2):121-38.
\2\ Andersson, F., The drug lag issue: the debate seen from an
international perspective, International Journal of Health Services,
1992; 22(1): 53-72.
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Since the beginning of the PDUFA program, there has been a
significant improvement in FDA funding for the drug review program,
including significant investments in information technology. PDUFA has
enabled FDA to virtually double the staff dedicated to the process of
reviewing human drug applications since 1992.
Under PDUFA, the industry provides additional funds through user
fees that are available to FDA, in addition to appropriated funds, to
spend on the human drug review process. Our authority to collect user
fees is ``triggered'' only when a base amount of appropriated funds,
adjusted for inflation, is spent.
In conjunction with PDUFA, FDA set review performance goals that
became more stringent each year. These goals applied to the review of
original new human drug and biological product applications,
resubmissions of original applications, and supplements to approved
applications. During the first few years of PDUFA I, we eliminated
backlogs of original applications and supplements that had formed in
earlier years when the program had fewer resources. Phased in over the
5 years of PDUFA I, the goals were to review and act on 90 percent of
priority new drug applications (NDAs), biologics license applications
(BLAs), and efficacy supplements (i.e., submissions for products
providing significant therapeutic gains) within 6 months of submission
of a complete application; to review and act on 90 percent of
nonpriority original NDAs, BLAs, and efficacy supplements within 12
months, and on resubmissions and manufacturing supplements within 6
months. Over the course of PDUFA I, we exceeded all of these
performance goals.
Under PDUFA II, some review performance goals continued to shorten.
For example, by 2002, the PDUFA II goals called on us to review and act
on 90 percent of the following:
Standard new drug and biological product applications and
efficacy supplements within 10 months,
Chemistry and manufacturing control supplements requiring
prior FDA approval within 4 months, and
Class 1 resubmissions (that respond to relatively minor
deficiencies such as labeling changes) within 2 months.
In addition, PDUFA II added a new set of goals intended to improve
our interactions with industry sponsors during the early years of drug
development, again with the goal of making promising new drug therapies
available to patients sooner. For example, these procedural goals
called for us to meet with sponsors and provide followup meeting
minutes within a certain number of days, and provide responses to
questions on industry submitted special study protocols within a
certain number of days. For example, PDUFA II goals called for us to
respond to 90 percent of industry requests:
Scheduling Type A meetings within 30-calendar days of FDA
receipt of the meeting request,
Scheduling Type B meetings within 60-calendar days of FDA
receipt of the meeting request,
Scheduling Type C meetings within 75-calendar days of FDA
receipt of the meeting request, and
Completing written assessments of the adequacy of special
protocols within 45 days of sponsor requests.
However, the agency experienced a much heavier review workload than
was accounted for by PDUFA II fee funding. By the end of PDUFA II, the
program was beginning to falter in terms of both performance and
financial stability. Although we were able to meet the letter of the
performance deadlines in many cases, FDA reviewers were not able to
allocate time for earlier and more frequent communication and feedback
to sponsors that might have resulted in better-quality applications and
a higher rate of first-cycle approvals.
Under the current program, reauthorized in 2002 (PDUFA III),
additional money from user fees was authorized to better finance the
expanded scope and growing volume of demand for FDA review and
consultation, and a mechanism was placed in PDUFA to annually adjust
fee revenues for increases in workload associated with the process for
the review of human drugs. For the first time, PDUFA III also
authorized FDA to spend user fee funds on certain aspects of postmarket
risk management. The review performance and procedural goals associated
with PDUFA III were similar to those under PDUFA II for FY 2002
performance levels, but the PDUFA III program addressed drug safety
issues and established several new initiatives to improve application
submissions and agency-sponsor interactions during drug development and
application review. The goals under PDUFA III included new provisions,
for example, to develop guidance for industry on good risk assessment,
risk management, and pharmacovigilance practices; to fund outside
expert consultants to help evaluate and improve review management
processes; and to centralize accountability and funding for all PDUFA
information technology initiatives and activities.
Furthermore, in conjunction with PDUFA's reauthorization in 2002,
FDA set the goal of creating a guidance for our review staff and
industry on good review management principles and practices (GRMPs) as
they apply to the first cycle review of NDAs, BLAs, and efficacy
supplements. We also set a goal of evaluating whether providing early
review of selected applications and additional feedback and advice to
sponsors during drug development for selected products can shorten drug
development and review times. Two ``continuous marketing application''
[[Page 1745]]
(CMA) pilot programs were initiated. CMA Pilot 1 provides for the
review of a limited number of presubmitted portions of NDAs and BLAs.
Under CMA Pilot 2, FDA and applicants can enter into agreements to
engage in frequent scientific feedback and interactions during the
investigational new drug phase of product development.
When it enacted PDUFA III, Congress enacted special provisions
regarding public accountability in the development of recommendations
for PDUFA IV. Congress directed FDA, when developing recommendations to
the Congress for PDFUA IV, to ``consult with the Committee on Energy
and Commerce of the House of Representatives, the Committee on Health,
Education, Labor, and Pensions of the Senate, appropriate scientific
and academic experts, health care professionals, representatives of
patient and consumer advocacy groups, and the regulated industry''
(Section 505. Accountability and Reports).
In preparing our proposed recommendations for PDUFA
reauthorization, we have conducted technical discussions with regulated
industry and have consulted with stakeholders as required by law. We
began our public consultation on PDUFA reauthorization with a public
meeting held on November 14, 2005 ( http://www.fda.gov/OHRMS/DOCKETS/98fr/05-20875.htm).
The meeting included presentations by FDA and a series of panels
representing different stakeholder groups, including patient advocates,
consumer groups, regulated industry, health professionals and academic
researchers. The stakeholders were asked to respond to the following
questions: (1) What is your assessment of the overall performance of
the PDUFA program thus far and (2) What aspects of PDUFA should be
retained, or what should be changed, to further strengthen and improve
the program?
There was general agreement among the responding stakeholders that
PDUFA should be reauthorized. Most expressed the view that drug review
should not only include safety and effectiveness review prior to
marketing approval, but also should encompass continued safety
monitoring after approval. Many panelists supported increased PDUFA
funds for postmarket drug safety surveillance, including developing and
monitoring risk management tools. A number of panelists also expressed
support for increased resources to fund the review of direct-to-
consumer (DTC) advertising. Some panelists expressed concern that over-
emphasizing safety might delay patient access to new treatments, and
some expressed support for PDUFA funding of ``Critical Path'' projects
to help speed new drug development (see http://www.fda.gov/oc/initiatives/criticalpath/).
In addition to our initial public meeting in November 2005, we held
followup meetings to obtain further input on the PDUFA program and
suggestions regarding what features should be proposed or amended with
program reauthorization.
On May 22, 2006, we held a meeting with patient advocacy groups.
Overall, these groups supported reauthorization of PDUFA as a vehicle
for speeding patient access to safe and effective drug therapies. They
also suggested that user fees be increased to sufficiently fund
postmarket safety activities and that the issues raised in the March
2006 GAO report entitled, ``Drug Safety: Improvement Needed in FDA's
Postmarket Decision-making and Oversight Process'' (GAO-06-402) http://www.gao.gov/new.items/d06402.pdf report on drug safety be addressed. In
addition, it was suggested that FDA establish postmarket performance
goals, such as milestones for development of a better postmarket safety
system.
On May 23, 2006, FDA held a meeting with consumer advocacy groups
to get their input on PDUFA reauthorization. Some consumer groups
indicated a preference for full funding of human drug review with
appropriated funds rather than user fees, but they generally considered
fee-funding to be inevitable and PDUFA reauthorization to be necessary.
Given this, the consumer advocacy groups who participated in the
meeting emphasized that user fees should be used to enable the agency
to adequately cover its priorities, but there should be no ties between
user fees and performance goals. They also expressed the view that
appropriated funding should be increased and there should be increased
funding to enhance FDA's capacity for postmarket safety and DTC
advertising review. Some consumer advocates further suggested that FDA
charge separate fees for DTC advertising review.
On June 23, 2006, we held a meeting with health professional groups
to obtain their views and suggestions for reauthorization. The health
professional groups supported PDUFA reauthorization to maintain an
efficient process and the availability of safe and effective new drugs
on the market. They also thought sufficient funding was needed to
maintain a competent scientific staff. The health professional groups
thought PDUFA fees should be increased to support safety surveillance
and risk management, and the current statutory time period for using
fee funds for safety-related work should be eliminated or expanded.
They also felt that fee-funded support for risk management plans should
be expanded to include older drugs as well as those recently approved.
They indicated that the issues raised in the March 2006 GAO report on
drug safety needed to be addressed. Finally, they suggested that PDUFA
funds be increased to support the review of DTC advertising.
Congress also directed FDA to publish in the Federal Register the
proposed recommendations developed through this process after
negotiations with the regulated industry, present the proposed
recommendations to the congressional committees specified in the
statute, hold a public meeting at which the public can present its
views on the proposed recommendations, and provide for a period of 30
days for the public to provide written comment on the proposed
recommendations.
We have now concluded discussions with industry and other
stakeholders regarding reauthorization of PDUFA. The purpose of this
document is to publish the recommendations we intend to propose to
Congress and announce the dates for the upcoming public meeting and
written comment period. After the public meeting and the close of the
30-day comment period, we plan to undertake a careful review of all
public comments on these proposed recommendations.
II. What We Are Proposing to Recommend for PDUFA IV
For PDUFA IV, as described in the following paragraphs, we plan,
with a few exceptions, to carry forward the performance goals from
PDUFA III and we propose additional goals related to proposed
enhancements to the program. Our proposed recommendations fall into
three major categories: (1) Proposals to ensure sound financial footing
for the human drug review program; (2) proposals to enhance the process
for premarket review of human drug applications; and (3) proposals to
modernize and transform the postmarket safety system. In addition, we
are proposing to recommend a program separate from, but related to,
PDUFA pertaining to fees assessed for advisory reviews of DTC
television advertisements. The summary table containing the proposals
and related fees under PDUFA IV can be found in table 1 of this
document. The discussion and additional fee estimates in this section
(II) and table 1 of this document,
[[Page 1746]]
do not include our proposals and proposed fee revenue figures for
review of DTC television advertisements. Those proposals are provided
in section III of this document.
Table 1.-- PDUFA IV Financial Baseline and Enhancements (starting in FY 2008)
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Financial Baseline Dollars FTE
----------------------------------------------------------------------------------------------------------------
FY 2007 Baseline-- $305,455,400 1539
Adjusted for
Inflation
----------------------------------------------------------------------------------------------------------------
Inflation $17,716,600 .............................................
Adjustment for FY
2008
----------------------------------------------------------------------------------------------------------------
Adjustment for $11,721,000 .............................................
Increased Rent
and Rent-Related
Costs
----------------------------------------------------------------------------------------------------------------
Adjustment for $20,000,000 87
Increased Work
per IND & NDA
PDUFA III
================================================================================================================
PDUFA IV Baseline $354,893,000 1626
Before
Enhancements
----------------------------------------------------------------------------------------------------------------
----------------------------------------------------------------------------------------------------------------
Enhancements
----------------------------------------------------------------------------------------------------------------
Premarket--Expedit $4,600,000 20
ing Drug
Development
----------------------------------------------------------------------------------------------------------------
Premarket--Improvi $4,000,000 .............................................
ng IT
Infrastructure
for Drug Review
----------------------------------------------------------------------------------------------------------------
Postmarket--Modern $29,290,000 82
izing and
Transforming
Safety System
================================================================================================================
PDUFA IV Total\1\ $392,783,000 1728
(in FY 2008)
----------------------------------------------------------------------------------------------------------------
\1\Further workload adjustment, to account for work levels in FY 2007, is expected to add about $45,000,000 and
195 FTEs for a final total of about $437,800,000 and 1923 FTEs for FY 2008.
A. Proposed Recommendations to Ensure Sound Financial Footing
Although user fees have provided substantial resources to FDA since
the beginning of the program, user fees have not kept up with the
increasing costs of the program associated with inflation in pay and
benefit costs to the agency, rent and rent-related costs, and workload.
Although the current law contains provisions for adjusting fees to
reflect the rate of inflation and changes in workload, we found that
the statutorily prescribed method for adjusting fees has not adequately
accounted for actual growth in costs and workload during PDUFA III. We
are proposing changes to the financial provisions of PDUFA to correct
for the shortcomings in these adjustment factors and place FDA on a
sound financial footing so we can continue with the program and make
enhancements to it.
1. Adjustment of Base Fee Revenue Amount for Growth in Cost and
Workload
Section 736(b) of the PDUFA provides the basic target fee revenue
amounts FDA uses to establish the application, product, and
establishment user fees each year. These target fee revenue amounts are
then adjusted for inflation and increases in workload, and the
resulting number becomes the amount FDA is authorized to collect in
fees. The statutory fee revenue amount for FY 2007 was $259,000,000.
Adjusted for inflation in accordance with PDUFA, that amount became
$305,455,400 for FY 2007. However, the PDUFA IV program will not begin
until FY 2008, so it was necessary to further adjust this number to
obtain the appropriate target revenues for FY 2008 before any
adjustments are made.
FDA's proposed recommendation to Congress resulting from industry
discussions is that the base target revenue estimate for FY 2008 should
be $392,783,000 and that this estimate should be further adjusted for
workload for FY 2007. FDA would calculate the workload adjustment based
on submissions through June 30, 2007, and publish the final amount and
supporting calculations when fees for FY 2008 are published. The
proposed target revenue estimate for FY 2008 includes the following
components:
The base revenue amount authorized in the current statute
for FY 2007, adjusted for inflation using provisions of the current
statute. This amount is $305,455,400.
An addition of $17,716,600 to adjust the base amount for
inflation for FY 2008. We assume a continuation of the average FDA
payroll and benefit cost inflation of 5.8 percent per year (see the
Inflation Adjustment discussion in section II.A.2.a of this document).
An addition of $11,721,000 to ensure that fees cover a
proportionate share of the increased costs that FDA will have to pay
for rent and rent-related costs and one-time costs of the required move
to the White Oak facility in Silver Spring, MD. These costs would be
added to the fee total to maintain the needed level of review staffing
(and associated direct costs) while also paying for these critical
nondiscretionary operating costs.
An addition of $20,000,000 to adjust the base amount of
fee revenues to cover significant increases in FDA's drug review
workload that occurred during PDUFA III, but were not captured by the
workload adjustment provision of PDUFA III and which we are
recommending be revised for PDUFA IV (see the Workload Adjustment
discussion in section II.A.2.b of this document). The PDUFA
[[Page 1747]]
III workload adjuster captured workload increases associated with
increased numbers of submissions, but did not capture workload
increases associated with the increased level of effort for each
submission. FDA documented that the review effort for each submission
increased significantly during PDUFA III. The investigational new drug
workload increased markedly because of significantly more meetings per
investigational new drug (IND) submitted and because of a sharp
increase in the number of special protocol assessments submitted for
FDA review.
An addition of $37,890,000 to fund the proposed
enhancements to the PDUFA program, including enhancements to the
premarket review program and proposals for modernizing and transforming
the postmarket safety system.
The sum of these components yields the proposed target revenue figure
of $392,783,000. ($392,883,000 = $305,455,400 + $17,716,600 +
$11,721,000 + $20,000,000 + $37,890,000).
2. Proposed Revisions to the Inflation Adjustment and Workload
Adjustment Applied to User Fees
(a) Inflation Adjustment: The fee revenue amounts for PDUFA III
were stated in FY 2003 dollars and the proposed fee revenue amounts for
PDUFA IV are stated in FY 2008 dollars. Before fees were assessed each
year in PDUFA III, the fee revenue target was increased and compounded
based on the higher of either: (1) The CPI/U over the latest 12-month
period or (2) the most recent increase in pay for Federal employees in
the Washington, D.C. area, compounded since FY 2003. The rate of pay
for employees in the Washington D.C. area was higher in all but one
year, and the PDUFA III inflation adjustment has resulted in average
annual inflation increases of 4.16 percent over each of the last 5
years. However, the actual cost of pay and benefits per full time
equivalent (FTE) is increasing faster than this factor. Data from the
past 5 years shows that the actual cost of salary and benefits has
increased at an average rate of 5.8 percent per year during the past 5
years for FDA. FDA proposes to recommend changing the provision for
calculation of the inflation adjustment to add to it a third factor--
FDA's actual rate of increase in the costs of pay and benefits per FTE
during the most recent 5-year period--and the annual adjustment would
be based on the highest of the three factors each year.
(b) Workload Adjustment: The workload adjuster currently applied in
PDUFA makes adjustments for changes in numbers of applications, but it
is flawed in two ways. First, the surrogate for IND workload in the
current workload adjuster is the number of new commercial INDs
submitted each year. Since each one of these INDs is active for several
years, the number of new applications submitted in any 1 year is a poor
surrogate for total IND workload. Second, the workload adjuster does
not take into account increases in work associated with active INDs,
NDAs, and BLAs. During PDUFA, there has been a substantial increase in
the numbers of meetings and special protocol assessments per IND
submission. However, the current workload adjuster only takes into
consideration changes in numbers of submissions--not additional
activity required per submission. Since FY 2002, the number of meetings
per commercial IND has increased by close to 30 percent, and the number
of special protocol assessments is up over 90 percent. This same
phenomenon occurs with NDAs as well, but to a somewhat lesser extent.
To remedy these flaws, the following changes are proposed: First,
we recommend changing the surrogate for IND workload in the statute
from the numbers of new commercial INDs received each year to the total
number of active commercial INDs each year. Active INDs are those that
have had at least one submission in the previous 12-month period.
Second, we recommend using an adjuster applied to the numbers of NDA/
BLAs and INDs. The proposed adjuster would adjust the numbers of these
applications in proportion to the impact on workload of increased
meetings and special protocol adjustments for INDs and for increased
meetings, labeling supplements, and annual reports for NDAs and BLAs.
Under the proposed change to the workload adjuster, we also propose
to contract with an independent accounting firm to examine the new
adjuster and make recommendations, if needed, for further improving
this adjuster.
3. Technical Changes to Increase Administrative Efficiency of the User
Fee Program
The FDA is proposing to recommend several technical changes to
PDUFA to simplify some of FDA's current procedures, to clarify the
original intent of several PDUFA definitions, and to remove potential
ambiguity. FDA's analysis of the impact of these changes indicates that
they would be revenue-neutral and would have a minimal impact on
industry fee-payers. These technical proposals include the following:
(a) Simplify the definition of ``human drug application'' to
include all new drug applications under section 505(b) of the Federal
Food, Drug, and Cosmetic Act;
(b) Amend the definition of ``small business'' for the purpose of
fee collection to reinstate language from the original PDUFA statute
that specifies that to qualify as a small business, the company may not
have an approved product already introduced in or delivered for
introduction into interstate commerce;
(c) Include capsules, tablets, and lyophilized products as examples
in the definition of final dosage form to provide clarification of what
constitutes a finished dosage form;
(d) Revise the waiver provisions to clarify that the person named
as the applicant and assessed the user fee is the person who is
eligible to request a waiver or reduction of fees;
(e) Change the date for the calculation of the adjustment factor so
it can be calculated before the President's budget goes to Congress;
(f) Clarify that for fee purposes, applications withdrawn before
filing will be treated as applications that FDA refuses to file, and
that they will be assessed a full fee if filed again or filed over
protest;
(g) For user fee purposes, reinstate the definition of ``person''
to include affiliates, as enacted under FDAMA
(h) Delay offsets for collections in excess of appropriations in
any year to the final year of the PDUFA program and make offsetting
reductions only if cumulative fees collected over the first 4 years
exceed cumulative appropriations for fees over the same period; and
(i) Revise the definition of ``prescription drug product'' for the
purpose of fee collection, to clarify the exclusion of products on
discontinued product lists maintained by Center for Drug Evaluation and
Research (CDER) and Center for Biologics Evaluation and Research
(CBER).
B. Enhancing the Process for Premarket Review
In the premarket review area, several changes were made in PDUFA
III as compared to PDUFA II. These are outlined as follows:
Continuous marketing application pilot programs: Two pilot
programs were established under PDUFA III to test whether providing
early review of selected applications and additional feedback and
advice to sponsors during drug development for selected products
[[Page 1748]]
can further shorten drug development and review times. Pilot 1 involved
a commitment on the part of FDA to review and provide feedback to the
sponsor within 6 months of submission of ``reviewable units'' of an
application in advance of the submission of the complete application.
This pilot program represented an extension of the ``rolling review''
program begun under FDAMA and was limited to applications that had
received a Fast Track designation. Pilot 2 involved a commitment on the
part of FDA to provide more structured and extensive interaction and
feedback to sponsors for up to one Fast Track application per review
division during drug development. This pilot represented an extension
of the usual interactions between FDA and sponsors during drug
development. To evaluate the costs and benefits of these pilots, FDA
commissioned an independent assessment. The CMA Pilot 1 Evaluation and
Pilot 2 Preliminary Evaluation Studies--Final Report is available on
the FDA Web site at http://www.fda.gov/ope/CMA/CMAFinalReport.pdf.
After review of the findings, FDA and industry representatives have
agreed that although the pilots demonstrated value in some areas, the
overall added benefits of the programs did not justify their costs to
FDA. Therefore, FDA is proposing to recommend that the CMA pilot
programs will not be continued in PDUFA IV.
First cycle review performance: In PDUFA III, FDA
committed to several new goals that were focused on improving the
effectiveness and efficiency of first cycle reviews in an attempt to
decrease the number of multi-cycle reviews without compromising FDA's
traditional high standards for approval. The first new goal was for FDA
to notify the applicant of any substantive deficiencies identified in
an application during the initial filing review. The identification of
such deficiencies was to be communicated to the applicant within 14
days of the 60-day application filing date, which is commonly known as
a ``74 day letter.'' FDA has consistently met or exceeded the goals for
communication of these early deficiencies. The second new goal was for
FDA to develop and publish a final joint CDER/CBER guidance on GRMPs.
FDA published a final GRMP final guidance on March 30, 2005, entitled,
``Guidance for Review Staff and Industry on Good Review Management
Principles and Practices for Prescription Drug User Fee Act Products;
Availability,'' at http://www.fda.gov/OHRMS/DOCKETS/98fr/05-6404.htm
(70 FR 16507; March 31, 2005). As part of the goals, FDA also committed
to develop and implement a training program for all CDER and CBER
review staff on the GRMPs. FDA met the goal for training all review
staff on the GRMPs and has incorporated training on the guidance as
part of new reviewer training. Finally, FDA committed to commission an
independent consultant evaluation of the factors associated with the
conduct of first cycle reviews. The first study was a retrospective
analysis of first cycle reviews for NME and original BLAs submitted in
FY2002-2004, and is available on the FDA Web site at http://www.fda.gov/ope/pdufa/PDUFA1stCycle/pdufa1stcycle.pdf. The second study
was a prospective study of first cycle reviews for NME and original BLA
submissions starting in FY05 and continuing through FY07, and is
currently in progress. FDA is proposing to recommend the continuation
of first cycle review performance initiatives.
Independent consultants for biotechnology clinical trial
protocols: This initiative allowed applicants for certain biotechnology
products to request that FDA engage an independent expert consultant,
selected by FDA, to participate in the agency's review of the protocol
for clinical studies that were expected to serve as the primary basis
for a claim. FDA has received no requests under this initiative during
PDUFA III and, after discussions with industry representatives, FDA is
proposing not to include this initiative in the recommended PDUFA IV
program.
1. Proposed Recommendations for Enhancement of Premarket Review Process
In the area of premarket review, FDA is proposing to recommend
enhancements in two areas: (1) Good review management principles and
(2) expediting drug development.
(a) Expanding Implementation of GRMPs: In the area of GRMPs, we are
proposing to recommend further enhancements associated with notifying
applicants at the time of the ``74-day letter'' of the anticipated
timeline for review of the application, including the anticipated date
for initiation of discussions regarding product labeling and any FDA
requests for postmarketing study commitments (PMCs).
Historically, labeling discussions have been initiated at the late
stages of a review, often in the last week before approval. Similarly,
the agency often communicates requests for postmarketing commitments
late in the review cycle. Initiation of discussion of these important
elements of the review of an application late in the review cycle is
often due to the inability of FDA to complete its review of the
application earlier because of an imbalance between workload and
available review staff time. Late initiation of these important
discussions is not consistent with the best practices that FDA has
identified and published in the GRMP guidance.
An understanding on the part of both the reviewers and the
applicant of the process and timeline for the review would facilitate
an efficient and scientifically sound review. FDA believes that
adhering to a timeline that includes earlier initiation of discussion
of labeling, coupled with the new physician labeling regulations (see
Requirements on Content and Format of Labeling for Human Prescription
Drug and Biological Products at http://www.fda.gov/OHRMS/DOCKETS/98fr/06-545.pdf) (71 FR 3922, January 24, 2006), would result in clearer,
more readily understandable labeling for new products. Furthermore, FDA
believes that initiation of discussions of possible postmarketing
commitments earlier in the process would allow for the commitments to
be more focused on the data needed to further inform the best use of
the products. We also expect that earlier discussion of PMCs would help
to ensure that the agreed to studies and study schedules are feasible,
thereby improving the timely completion of the studies by the
applicant.
The proposed recommendations under the enhancements for GRMP are
also intended to encourage applicants to provide FDA with applications
that are complete for review at the time of submission. The submission
of complete applications would allow FDA to effectively manage and
adhere to its review schedule and, ultimately, may result in faster
access to these new products without any compromise to FDA's
traditional high standards for approval. Consequently, FDA believes
these proposed recommendations to be in the best interest of the
agency, the applicant, and, ultimately, the public health.
(b) Expediting drug development: One of the things that the agency
can do to enhance the development of new and beneficial drugs is to
provide guidance to industry to clarify current agency thinking on a
variety of topics including, among other things, clinical trial design.
Our experience and insight, gained through years of review, can help
the industry avoid wasting scarce research and development resources on
clinical trials that are not likely to produce results because of
flawed designs. By clarifying the agency's
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expectations regarding the nature of data needed to support certain
types of claims, we can allow the industry to focus their efforts on
useful trials and decrease less useful experimentation. This would have
the benefit of decreasing exposure of subjects to unapproved products,
decreasing the amount of time required to bring a beneficial new drug
to market, and, possibly, decreasing the total cost of bringing the new
drug to market, which should translate to lower drug prices for the
consumer.
Guidance development by the agency requires substantial time
commitments from those who are already heavily involved in the review
effort. The PDUFA IV proposal includes increased user fees that would
be used to fund additional staff resources to develop the following
guidances to enhance clinical drug development (the FY dates for each
guidance represent FDA's proposed commitment to publish a draft
guidance on that topic by no later than the end of FY listed):
1. Clinical Hepatotoxicity--FY 2008. This guidance would address
how to evaluate a drug for possible hepatotoxicity during drug
development and how FDA will review an application to look for signs
that a drug may be a significant hepatotoxin.
2. Non-inferiority Trials--FY 2008. This guidance would describe
FDA's perspective on the design of noninferiority trials. Topics
addressed are expected to include how to select the active control, how
to document the effect size of the active control versus placebo, and
how to establish the noninferiority margin of interest.
3. Adaptive Trial Designs--FY 2008. This guidance would explain
FDA's perspective on the use of adaptive trial designs during drug
development. Topics to be addressed include the definition of adaptive
trial designs, recommended designs, and how the statistical issues
should be addressed in analyzing trials.
4. End of Phase 2(a) Meetings--FY 2008. This guidance would outline
the procedures and data needed for an end-of-phase 2a (EOP2a) meeting.
The EOP2a meetings are intended to facilitate FDA interactions with a
sponsor earlier in the design of the development program to maximize
the value of the phase 2 program with the overall goal of making drug
development more efficient and effective.
5. Multiple Endpoints in Clinical Trials--FY 2009. This guidance
would describe FDA's perspective on the appropriate procedures and
analyses for trials with multiple endpoints (e.g., a trial with
multiple co-primary endpoints).
6. Enriched Trial Designs--FY 2010. This guidance would focus on
approaches to enrich the clinical trial population to better define the
efficacy or safety of the drug under development.
7. Imaging Standards for Use as an End Point in Clinical Trials--
FY 2011. This guidance would focus on the use of images as important
endpoints in controlled clinical trials. Issues would include image
acquisition, archiving, and blinded reading.
The commitment, under this part of the proposed PDUFA IV program,
would allow us to pursue the development and publication of several
guidance documents to facilitate the development of new, life-saving
therapies, moving them more efficiently from the laboratory to the
bedside.
In addition to funding the development of guidances, under PDUFA IV
we are proposing to collect user fees to hire additional staff to free
up reviewer time to enable greater participation in scientific research
collaborations that will ultimately help clarify regulatory pathways
for new technologies and potential new biomarkers for drug safety and
effectiveness. For example, FDA intends to participate in workshops
with representatives from the scientific community (including industry,
academia, and other interested stakeholders) to further the science
toward development of guidance documents in the following areas:
1. Predictive toxicology--Emerging science such as toxicogenomics,
proteomics, metabolomics, and molecular imaging, is expected to yield
more sensitive, specific, and informative tests for drug organ toxicity
than the toxicology screening techniques currently in use. FDA
reviewers will need to participate extensively in the design of studies
intended to qualify these new safety tests for regulatory uses.
2. Biomarker Qualification--Biomarkers are frequently used during
drug development to understand the effect of a drug on biologic systems
and to predict clinical response. Before biomarkers can be used for
regulatory decision making they must be qualified. FDA expertise will
be needed on an ongoing basis in the effort to select and test
candidate biomarkers for qualification. FDA reviewers will need to
participate in the design of the definitive studies intended to qualify
the biomarker for a specific regulatory use.
3. Missing Data--In controlled clinical trials it is often
impossible to ensure that every data element described in the protocol
is collected for every study subject. For example, subjects often
discontinue participation in a trial early and do not return for
further study visits. The question of how to handle missing data when
analyzing the results of a trial is a very complex one, and FDA would
expect to work in collaboration with outside stakeholders to further
explore the science of this issue and develop appropriate procedures.
Finally, under the proposal for PDUFA IV, user fees would be used
to support FDA participation in workshops and other public meetings to
explore new approaches to a structured model for benefit/risk
assessment. The results of these interactions would be used to assess
whether pilot(s) of such new approaches can be conducted during PDUFA
IV. These efforts may lead to the development of guidance documents.
Under PDUFA IV, FDA proposes to collect an additional $4,600,000 in FY
2008 and, in subsequent years, adjusted for inflation and workload, to
support at least 20 FTEs to engage in the collaborations with outside
stakeholders described previously.
2. Improving the IT Infrastructure for Human Drug Review
Under PDUFA III, we agreed to certain performance goals associated
with better management of information technology (IT) resources and
improved consistency of IT practices across the human drug review
program. Under PDUFA III, we centralized accountability for PDUFA IT
funding under the Chief Information Officer (CIO); established an IT
Project Management Office to develop and implement processes policies,
based on the Capability Maturity Model Integration process improvement
approach to improve software development practices; implemented the
electronic Common Technical Document standard for electronic regulatory
submissions; established a common secure single point of entry for the
receipt and processing of all electronic submissions, commonly called
the FDA Electronic Submissions Gateway; and established a common
approach to managing desktop hardware and software configurations. We
are now in the process of establishing a common approach for secure e-
mail that will be implemented throughout the PDUFA program. Following
provisions in the PDUFA III commitment letter, we have also met
quarterly with industry representatives to discuss progress
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towards these IT goals and to address technical implementation issues.
These accomplishments have built a strong foundation for further
progress toward an IT environment that better serves the human drug
review program.
Under PDUFA IV, we recommend collection of an additional $4,000,000
annually, starting in FY 2008 to enable the agency to commit to several
IT performance goals that would move FDA and industry towards an all-
electronic environment, which would increase the efficiency of the
review process. Under these proposed goals, we would commit to develop
a 5-year IT plan that would lay out the technical approach for
achieving a more integrated, standards-based electronic regulatory
submission and review environment. The plan would help FDA, industry,
and stakeholders make related IT investments in a more coordinated
manner. By the end of PDUFA IV, following implementation of these
proposed goals, human drug application sponsors would be able to send
in their electronic applications with automated cross-links to
previously submitted data and information, so that they only have to
submit things once. In addition, FDA reviewers would be able to
retrieve all relevant submissions and related data electronically from
their work stations and would have efficient tools for searching and
analyzing data to support their reviews. These capabilities would
enable more efficient and reliable management of regulatory
submissions.
By the end of PDUFA IV, if resources are provided as expected, we
intend to have the capability to handle two-way transmission of
regulatory correspondence with industry, which would accelerate the
movement toward an all-electronic submission and review environment.
To determine whether we are moving towards achieving the IT goals
described in PDUFA IV, we further propose to track several key
performance indicators of the adoption rate of electronic submissions
and the technical error rates associated with those submissions, so
that we can more closely monitor progress toward the all-electronic
environment.
Finally, in the recommended IT performance goals for PDUFA IV, we
propose a cost-effective approach that minimizes expenditures on
existing legacy systems and redirects those funds toward the
development of new common systems that are better coordinated and more
flexible.
C. Modernizing and Transforming the Postmarket Drug Safety System
In PDUFA III, for the first time, FDA was authorized to spend user
fees revenues to fund improvements in drug safety. This change provided
important new resources to help improve postmarket safety but our
experience has shown that further improvements can be achieved. The
definition of the ``process for the review of human drug applications''
in section 735 of PDUFA describes which products PDUFA funds can be
used for in terms of postmarket safety review as well as the length of
time after product approval PDUFA funds can be used for such safety
review. Specifically, 735(6)(F) states: ``In the case of drugs approved
after October 1, 2002, under human drug applications or supplements:
collecting, developing, and reviewing safety information on the drugs,
including adverse event reports, during a period of time after approval
of such applications or supplements, not to exceed three years.''
In addition, the PDUFA III Reauthorization Performance Goals and
Procedures document stated that user fees may be used ``for a period of
up to two years post-approval for most products and for a period of up
to three years for products that require risk management beyond
standard labeling * * *.'' The stated purpose of this language was to
provide user fees to review an applicant's implementation of risk
management plans for this period of time and to allow for evaluation of
study reports, product use, and other safety activities. Drug safety
activities outside of the specified timeframe were to be funded with
appropriated dollars.
As part of the PDUFA IV program, we propose to recommend further
enhancing the program by removing the language that limits the spending
of user fees outside of the specified timeframe. Current data show that
safety issues can arise after a drug has been on the market for 8 or
more years. A recent FDA analysis of safety-related label changes made
between October 2002 and August 2005, for all drug products with a
labeling change, found that the total number of safety-related label
changes exceeded 160 changes for drugs 3 years postapproval and
remained at or above that high level until 8 years postapproval before
starting to decline. All stakeholders agree that the current
limitations on use of funds for postmarketing safety-related activities
present an opportunity for improving the agency's ability to optimally
support adverse event surveillance, detection, evaluation, and
management. Enhancing the program by eliminating such limitations would
help both FDA and drug sponsors because safety assessments of drug
products by both FDA and sponsors are necessary for drugs over time to
adequately manage risks, regardless of approval date. Increased
resources, including from PDUFA funds, would enable FDA to engage in
safety review activities, such as studies of drugs in the same class
approved before and after October 1, 2002, to adequately assess
significant drug safety issues. The current description of
postmarketing safety activities in the definition of the ``process for
the review of human drug applications'' could also be revised to better
reflect the broad variety of activities that are important to
postmarket safety review.
As part of the reauthorization of PDUFA, FDA proposes changing the
statute to eliminate the statutory restrictions so that PDUFA fees
could be used to assess safety issues postapproval, independent of a
product's approval date and would allow the agency to review the drug's
safety in whatever time frame risks arise using all available
resources. This change would provide much needed support for timely,
predictable, consistent, and scientifically sound regulatory
decisionmaking and would work towards a fully integrated evaluation of
drugs and biologics throughout their life cycle.
In addition, we propose expanding the description of postmarket
safety activities to capture a broader range of activities related to
postmarket safety review. For example, FDA would use $29,290,000 in new
user fee funds to enhance and modernize the current U.S. drug safety
system. We would adopt new scientific approaches, improve the utility
of existing tools for the detection, evaluation, prevention, and
mitigation of adverse events associated with drugs and biological
products. In addition, FDA would use these funds to continue to enhance
and improve communication and coordination between pre- and postmarket
review staff. Potential activities in this area might include
integration of certain proposed recommendations made by the Institute
of Medicine (IOM) in their September 2006 report entitled, ``The Future
of Drug Safety: Promoting and Protecting the Health of the Public.''
PDUFA IV funds would also be used to support a number of activities
designed to modernize the process of pharmacovigilance. One key
initiative would be the implementation of an FDA contract to one or
more outside research organization(s) to conduct research on
[[Page 1751]]
determining the best way to maximize the public health benefits
associated with collecting and reporting serious and nonserious adverse
events occurring throughout a product's life cycle. Studies under this
contract would answer such central questions as the number and types of
safety concerns that are discovered by various types of adverse event
collection, the age of the medical products at the time such safety
concerns are detected, and the types of actions that are subsequently
taken and their ultimate effect on patient safety.
PDUFA IV funds would also support the development of a guidance
document to delineate epidemiology best practices. Epidemiologic
studies using large automated databases are increasingly being
performed to evaluate drug safety. These studies and safety analyses
are complex and employ a variety of nonstandardized analytic methods
and assumptions. During the course of PDUFA IV, FDA, with input from
academia, industry, and others from the general public, would hold a
public workshop to identify best practices in this emerging field,
ultimately developing a document that addresses epidemiology best
practices and provides guidance on how to carry out scientifically
sound observational studies using quality data resources.
Another critical part of the transformation of the drug safety
program would be maximizing the usefulness of tools used for adverse
event detection and risk assessment. To achieve this end, data other
than spontaneous adverse event reports, including population-based
epidemiological data and other types of observational data resources,
would be used and evaluated. Access to these types of data would expand
our capability to carry out targeted postmarketing surveillance, look
at class effects of drugs, and potentially carry out signal detection
using data resources other than reports from FDA's adverse event
reporting system (AERS). PDUFA IV funds would be used to obtain access
to additional databases and increase program staffing with
epidemiologists, safety evaluators, and programmers who can use these
new resources.
As mentioned previously, the PDUFA III Reauthorization Performance
Goals and Procedures document provided user fees to review
implementation of a risk management plans for a limited period of time
and to allow for evaluation of study reports, product use, and other
safety activities. Risk communication and management have now become a
routine part of human drug review, yet many of the risk management and
risk communication tools the industry uses remain unproven and
unstandardized. To promote more effective and consistent use of these
tools to mitigate the risk of drugs and biological products, under
PDUFA IV, with input from academia, industry, and others from the
general public, we would conduct an annual systematic public discussion
and review of the effectiveness of one to two risk management programs
and one major risk management tool per year. Reports from these
discussions would be posted on the FDA Web site.
FDA would also use PDUFA IV fees to enhance the agency's AERS and
surveillance tools, to strengthen its IT infrastructure to support
access and analyses of externally linked databases, and to support a
safety workflow tracking system. This support for drug and biological
product safety-related IT systems is critical to ensure the best
collection, evaluation, and management of the vast quantity of safety
data received by FDA.
FDA would use PDUFA IV funds to develop and periodically update a
5-year plan describing the range of activities designed to enhance and
modernize the drug safety system. FDA would publish and seek public
comment on an initial plan for these activities and conduct an annual
assessment of progress against the plan to be published on FDA Web
site. In addition to progress against the specific modernization
activities described previously, the annual report would include an
update on FDA efforts to facilitate the interactions between the Office
of New Drugs and the Office of Surveillance and Epidemiology related to
the process of evaluating and responding to postmarketing drugs safety/
adverse event reports. FDA would publish updates to the modernization
plan as FDA deems necessary and post on FDA's Web site draft revisions
to the plan, soliciting comments from the public on those draft
revisions and then carefully considering all public comments before
completing and publishing updates to the plan.
Another recent study by the IOM, entitled ``Preventing Medication
Errors: Quality Chasm Series,'' (July 20, 2006), estimates that, on
average, every hospitalized patient is subject to at least one
medication error per day. These errors lead to costly morbidity and
mortality. The IOM concluded that drug names that look or sound
similar, in addition to the layout and presentation of important drug
information on the label, labeling, and packaging of drug products
increase the risk of medication errors. The IOM report recommended that
the FDA, the pharmaceutical industry, and other stakeholders should
collaborate in several areas to improve methods for naming and labeling
drug products and communicating medication information to providers and
consumers and advised the FDA to develop guidance documents for
industry related to drug naming, labeling, and packaging.
Using PDUFA IV funds, FDA would implement various measures to
reduce medication errors related to look-alike and sound-alike
proprietary names as well as factors such as unclear label
abbreviations, acronyms, dose designations, and error-prone label and
packaging designs. Activities to be funded include guidance
development, review performance goals, and initiation of a pilot
program to explore a different paradigm for proprietary name review.
Fees would provide the resources FDA needs to publish three
guidances to industry: (1) Guidance on the contents of a complete
submission package for a proposed proprietary drug/biological product
name; (2) guidance on best practices for naming, labeling, and
packaging drugs and biologics to reduce medication errors; and (3)
guidance on proprietary name evaluation best practices. These
guidances, developed after consultation with industry, academia, and
others from the general public, would provide a scientifically sound
and consistent approach to the selection, evaluation, and review of
proprietary names and would also create a framework for best practices
for the layout and design of drug labels and packaging to prevent or
minimize medication errors.
In addition, under the proposed PDUFA IV program, FDA would commit
to a performance goal of 180 days for reviewing proprietary names
submitted during the IND and NDA phases. For submissions received as
part of an IND, submitted as early as the end of phase 2 of drug
development, FDA would increase the percentage of submissions subject
to this goal, from 50 percent in year 1 to 90 percent in year 4 of the
program. In a similar phased-in fashion, for submissions received as
part of an NDA or BLA, FDA would review 50 percent (in year 1)
increasing to 90 percent (in year 4) of proprietary name submissions
within 90 days of receipt. Commitment to review goals would enhance the
timeliness and predictability of proprietary name review.
During PDUFA IV, FDA proposes to develop and implement a pilot
program that shifts the responsibility for testing proposed proprietary
names from FDA to the pharmaceutical industry. This
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program would enable pharmaceutical firms participating in the pilot to
evaluate proposed proprietary names and submit the data generated from
those evaluations to FDA for review prior to approval. Using this more
traditional FDA review role was recommended by the IOM in November 1999
report, entitled ``To Err Is Human: Building a Safer Health System, ''
as well as the HHS Advisory Committee on Regulatory Reform in November
of 2002 Secretary's Advisory Committee on Regulatory Reform, November
21, 2002, http://regreform.hhs.gov/meetinginfo/november_meetinginfo.htm. The proposed pilot would allow this approach to be
evaluated for its contribution to the efficiency and timeliness of
proprietary name review.
III. What We Are Proposing to Recommend for Review of Direct-To-
Consumer Advertising
In addition to our proposed recommendations for enhancements to the
current human drug review program, we are proposing to recommend a
program separate from, but related to, PFUFA assessing fees for
advisory reviews of DTC television advertisements. Research has shown
there can be benefits associated with DTC prescription drug television
advertising, such as informing patients about the availability of new
treatment options and encouraging patients to see a physician about an
illness for the first time. Notwithstanding these benefits, concerns
have arisen about the effects of DTC television advertisements on
prescribing practices and prescription drug use. Companies have the
option of submitting their proposed advertisements to FDA for advisory
review before publicly disseminating them, which gives them with the
benefit of FDA input on whether or not the advertisements are accurate,
balanced, and adequately supported, enabling them to address any
problems before the advertisements are shown to the public, thus
improving the quality of the advertisements.
Companies recognize the benefits this advisory review mechanism
offers. In fact, PhRMA recently stated in its voluntary guidance
principles on DTC advertising that companies should submit all new DTC
television advertisements to FDA before broadcasting them http://www.phrma.org/files/DTCGuidingprinciples.pdf. However, although FDA's
DTC advisory review workload has been steadily increasing, staffing for
this activity has remained level. As a result, it is impossible for FDA
to review all of the DTC television advertisement advisory submissions
it receives in a timely manner. The lack of timely, predictable FDA
review times for DTC television advertisements is detrimental to
companies' ability to accurately set timeframes for their marketing
campaigns and discourages companies from submitting these materials for
advisory review.
We propose creating a separate program, not directly included under
PDUFA IV, to assess, collect, and use fees for the advisory review of
prescription drug television advertisements. These user fees would not
be funded by application, product, or establishment fees assessed under
PDUFA. Instead, these new fees would be assessed separately and
collected only from those companies that intend to seek FDA advisory
reviews of DTC television advertisements. The proposed recommendation
for fee funding and the estimated number of supported staff are
summarized in table 2 of this document.
Table 2.--Proposed Fees for DTC Advertisement Review (starting in FY 2008)
----------------------------------------------------------------------------------------------------------------
Proposed Program Dollars FTE
----------------------------------------------------------------------------------------------------------------
----------------------------------------------------------------------------------------------------------------
Advisory Review of $6,250,000 27
DTC Television
Advertisements
----------------------------------------------------------------------------------------------------------------
Program Total (in $6,250,000 27
FY 2008)
----------------------------------------------------------------------------------------------------------------
This program would provide for increased FDA resources to allow for
the timely review of DTC television advertisement advisory submissions.
To ensure stable funding for the program in case the number of advisory
submissions fluctuates widely from year to year, the program would
assess a one-time participation fee. The program would then charge fees
each year for each advisory review requested. These new fees would
provide sufficient resources for FDA to hire additional staff to review
DTC television advisory submissions in a predictable, timely manner.
FDA anticipates collecting $6.25 million in annual fees during the
first year of the program (and a similar amount to go into the reserve
fund) to support 27 additional staff to review DTC television
advertising. Advisory review fee amounts would be adjusted annually for
inflation and to take into account increases in workload. As part of
this program, FDA is proposing to commit to certain performance goals
including review of a certain number of original advisory review
submissions in 45 days and resubmissions in 30 days. The goals would be
phased in over the 5 years of the program to allow for recruitment and
training of staff.
IV. What Information Should You Know About the Meeting?
A. When and Where Will the Meeting Occur? What Format Will We Use?
Through this document, we are announcing the convening of a public
meeting to hear stakeholder views on the recommendations we propose to
provide to Congress on the reauthorization of PDUFA IV.
We will conduct the meeting on February 16, 2007, at the Grand
Hyatt Washington at Washington Center (see ADDRESSES). In general, the
meeting format will include presentations by FDA and a series of panels
representing different stakeholder interest groups (such as patient
advocates, consumer advocates, industry, health professionals, and
academic researchers). We will also give individuals the opportunity to
make presentations at the meeting, and for organizations and
individuals to submit written comments to the docket after the meeting.
B. How Do You Register for the Meeting or Submit Comments?
If you wish to attend and/or make a presentation at the meeting,
please send an electronic mail message to
[email protected] by February 2, 2007. Your e-mail
should include the following information: Name, Company, Company
Address, Company Phone Number, and E-mail Address. You will receive a
confirmation within 2 business days.
[[Page 1753]]
We also will accept walk-in registration at the meeting site, but
space is limited, and we will close registration when maximum seating
capacity (approximately 500) is reached.
We will try to accommodate all persons who wish to make a
presentation. The time allotted for presentations may depend on the
number of persons who wish to speak
Additionally, regardless of whether you wish to make a presentation
or simply attend the meeting, please notify us if you need any special
accommodations (such as wheelchair access or a sign language
interpreter).
If you would like to submit comments regarding these proposed
recommendations, please send your comments to the Division of Dockets
Management (see ADDRESSES). Submit a single copy of electronic comments
or two paper copies of any written comments, except that individuals
may submit one paper copy. Comments are to be identified with the
docket number found in brackets in the heading of this document.
Received comments may be seen in the Division of Dockets Management
between 9 a.m. and 4 p.m., Monday through Friday.
To ensure consideration of your comments, you should send your
comments no later than February 23, 2007.
C. Will Meeting Transcripts Be Available?
We will prepare a meeting transcript and make it available on our
Web site (www.fda.gov) after the meeting. We anticipate that
transcripts will be available approximately 30 business days after the
meeting. The transcript will also be available for public examination
at the Division of Dockets Management (HFA-305), 5630 Fishers Lane, rm.
1061, Rockville, MD 20852, between 9 a.m. and 4 p.m. Monday through
Friday.
Dated: January 10, 2007.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 07-122 Filed 1-11-07; 8:45 am]
BILLING CODE 4160-01-S