[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: <a href="/cdn-cgi/l/email-protection#175679793944627b7b7e61767957717376397f7f6439707861"><span class="__cf_email__" data-cfemail="31705f5f1f62445d5d5847505f715755501f5959421f565e47">[email protected]</span></a>.
    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:
    <bullet> Standard new drug and biological product applications and 
efficacy supplements within 10 months,
    <bullet> Chemistry and manufacturing control supplements requiring 
prior FDA approval within 4 months, and
    <bullet> 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:
    <bullet> Scheduling Type A meetings within 30-calendar days of FDA 
receipt of the meeting request,
    <bullet> Scheduling Type B meetings within 60-calendar days of FDA 
receipt of the meeting request,
    <bullet> Scheduling Type C meetings within 75-calendar days of FDA 
receipt of the meeting request, and
    <bullet> 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)
----------------------------------------------------------------------------------------------------------------
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:
    <bullet> 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.
    <bullet> 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).
    <bullet> 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.
    <bullet> 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.
    <bullet> 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:
    <bullet> 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.
    <bullet> 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.
    <bullet> 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

[[Page 1749]]

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

[[Page 1750]]

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

[[Page 1752]]

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 
<a href="/cdn-cgi/l/email-protection#a0e3e2e5f2f4d2c1c9cec9cec7f3d5c7c7c5d3d4c9cfced3e0c6c4c18ec8c8d38ec7cfd6"><span class="__cf_email__" data-cfemail="5f1c1d1a0d0b2d3e36313631380c2a38383a2c2b3630312c1f393b3e7137372c71383029">[email protected]</span></a> 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


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