Federal Register / Vol. 72, No. 9 / Tuesday, January 16, 2007 / Notices 1743 

Certification Regarding Drug-Free 

Workplace Requirements 

Alternate I. (Grantees Other Than 

Individuals) 

The grantee certifies that it will or will 

continue to provide a drug-free workplace by: 

(a) Publishing a statement notifying 

employees that the unlawful manufacture, 

distribution, dispensing, possession, or use of 

a controlled substance is prohibited in the 

grantee’s workplace and specifying the 

actions that will be taken against employees 

for violation of such prohibition; 

(b) Establishing an ongoing drug-free 

awareness program to inform employees 

about—

(1) The dangers of drug abuse in the 

workplace; 

(2) The grantee’s policy of maintaining a 

drug-free workplace; 

(3) Any available drug counseling, 

rehabilitation, and employee assistance 

programs; and 

(4) The penalties that may be imposed 

upon employees for drug abuse violations 

occurring in the workplace; 

(c) Making it a requirement that each 

employee to be engaged in the performance 

of the grant be given a copy of the statement 

required by paragraph (a); 

(d) Notifying the employee in the statement 

required by paragraph (a) that, as a condition 

of employment under the grant, the employee 

will—

(1) Abide by the terms of the statement; 

and 

(2) Notify the employer in writing of his or 

her conviction for a violation of a criminal 

drug statute occurring in the workplace no 

later than five calendar days after such 

conviction; 

(e) Notifying the agency in writing, within 

10 calendar days after receiving notice under 

paragraph (d)(2) from an employee or 

otherwise receiving actual notice of such 

conviction. Employers of convicted 

employees must provide notice, including 

position title, to every grant officer or other 

designee on whose grant activity the 

convicted employee was working, unless the 

Federal agency has designated a central point 

for the receipt of such notices. Notice shall 

include the identification number(s) of each 

affected grant; 

(f) Taking one of the following actions, 

within 30 calendar days of receiving notice 

under paragraph (d)(2), with respect to any 

employee who is so convicted —

(1) Taking appropriate personnel action 

against such an employee, up to and 

including termination, consistent with the 

requirements of the Rehabilitation Act of 

1973, as amended; or 

(2) Requiring such employee to participate 

satisfactorily in a drug abuse assistance or 

rehabilitation program approved for such 

purposes by a Federal, State, or local health, 

law enforcement, or other appropriate 

agency; 

(g) Making a good faith effort to continue 

to maintain a drug-free workplace through 

implementation of paragraphs (a), (b), (c), (d), 

(e) and (f). 

(B) The grantee may insert in the space 

provided below the site(s) for the 

performance of work done in connection 

with the specific grant: 

Place of Performance (Street address, city, 

county, state, zip code) . 

lllllllllllllllllllll

lllllllllllllllllllll

Check if there are workplaces on file that 

are not identified here. 

Alternate II. (Grantees Who Are Individuals) 

(a) The grantee certifies that, as a condition 

of the grant, he or she will not engage in the 

unlawful manufacture, distribution, 

dispensing, possession, or use of a controlled 

substance in conducting any activity with the 

grant; 

(b) If convicted of a criminal drug offense 

resulting from a violation occurring during 

the conduct of any grant activity, he or she 

will report the conviction, in writing, within 

10 calendar days of the conviction, to every 

grant officer or other designee, unless the 

Federal agency designates a central point for 

the receipt of such notices. When notice is 

made to such a central point, it shall include 

the identification number(s) of each affected 

grant. 

[FR Doc. E7–374 Filed 1–12–07; 8:45 am] 

BILLING CODE 4184–01–P 

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. 

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: 

Ann.Sullivan@fda.hhs.gov. 

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 


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1744 Federal Register / Vol. 72, No. 9 / Tuesday, January 16, 2007 / Notices 

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. 

2Andersson, F., The drug lag issue: the debate 

seen from an international perspective, 

International Journal of Health Services, 1992; 

22(1): 53–72. 

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. 

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’’


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(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, 


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1746 Federal Register / Vol. 72, No. 9 / Tuesday, January 16, 2007 / Notices 

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—Adjusted for Inflation $305,455,400 1539 

Inflation Adjustment for FY 2008 $17,716,600 

Adjustment for Increased Rent and 

Rent-Related Costs $11,721,000 

Adjustment for Increased Work per 

IND & NDA PDUFA III $20,000,000 87 

PDUFA IV Baseline Before Enhancements $354,893,000 1626 

Enhancements 

Premarket—Expediting Drug Development $4,600,000 20 

Premarket—Improving IT Infrastructure for Drug Review $4,000,000 

Postmarket—Modernizing and Transforming Safety System $29,290,000 82 

PDUFA IV Total1 (in FY 2008) $392,783,000 1728 

1Further 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 


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Federal Register / Vol. 72, No. 9 / Tuesday, January 16, 2007 / Notices 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 revenueneutral 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 


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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 endof-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 allelectronic 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 allelectronic 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 


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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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1752 Federal Register / Vol. 72, No. 9 / Tuesday, January 16, 2007 / Notices 

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-ToConsumer 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 DTC Television 

Advertisements $6,250,000 27 

Program Total (in FY 2008) $6,250,000 27 

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 onetime 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 

CBERTrainingSuggestions@fda.hhs.gov 

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. 


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Federal Register / Vol. 72, No. 9 / Tuesday, January 16, 2007 / Notices 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 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Substance Abuse and Mental Health 

Services Administration 

Current List of Laboratories Which 

Meet Minimum Standards To Engage in 

Urine Drug Testing for Federal 

Agencies 

AGENCY: Substance Abuse and Mental 

Health Services Administration, HHS. 

ACTION: Notice. 

SUMMARY: The Department of Health and 

Human Services (HHS) notifies Federal 

agencies of the laboratories currently 

certified to meet the standards of 

Subpart C of the Mandatory Guidelines 

for Federal Workplace Drug Testing 

Programs (Mandatory Guidelines). The 

Mandatory Guidelines were first 

published in the Federal Register on 

April 11, 1988 (53 FR 11970), and 

subsequently revised in the Federal 

Register on June 9, 1994 (59 FR 29908), 

on September 30, 1997 (62 FR 51118), 

and on April 13, 2004 (69 FR 19644). 

A notice listing all currently certified 

laboratories is published in the Federal 

Register during the first week of each 

month. If any laboratory’s certification 

is suspended or revoked, the laboratory 

will be omitted from subsequent lists 

until such time as it is restored to full 

certification under the Mandatory 

Guidelines. 

If any laboratory has withdrawn from 

the HHS National Laboratory 

Certification Program (NLCP) during the 

past month, it will be listed at the end, 

and will be omitted from the monthly 

listing thereafter. 

This notice is also available on the 

Internet at http://workplace.samhsa.gov 

and http://www.drugfreeworkplace.gov. 

FOR FURTHER INFORMATION CONTACT: Mrs. 

Giselle Hersh or Dr. Walter Vogl, 

Division of Workplace Programs, 

SAMHSA/CSAP, Room 2–1035, 1 Choke 

Cherry Road, Rockville, Maryland 

20857; 240–276–2600 (voice), 240–276–

2610 (fax). 

SUPPLEMENTARY INFORMATION: The 

Mandatory Guidelines were developed 

in accordance with Executive Order 

12564 and section 503 of Public Law 

100–71. Subpart C of the Mandatory 

Guidelines, ‘‘Certification of 

Laboratories Engaged in Urine Drug 

Testing for Federal Agencies,’’ sets strict 

standards that laboratories must meet in 

order to conduct drug and specimen 

validity tests on urine specimens for 

Federal agencies. To become certified, 

an applicant laboratory must undergo 

three rounds of performance testing plus 

an on-site inspection. To maintain that 

certification, a laboratory must 

participate in a quarterly performance 

testing program plus undergo periodic, 

on-site inspections. 

Laboratories which claim to be in the 

applicant stage of certification are not to 

be considered as meeting the minimum 

requirements described in the HHS 

Mandatory Guidelines. A laboratory 

must have its letter of certification from 

HHS/SAMHSA (formerly: HHS/NIDA) 

which attests that it has met minimum 

standards. 

In accordance with Subpart C of the 

Mandatory Guidelines dated April 13, 

2004 (69 FR 19644), the following 

laboratories meet the minimum 

standards to conduct drug and specimen 

validity tests on urine specimens: 

ACL Laboratories, 8901 W. Lincoln 

Ave., West Allis, WI 53227, 414–328–

7840 / 800–877–7016 (Formerly: 

Bayshore Clinical Laboratory). 

ACM Medical Laboratory, Inc., 160 

Elmgrove Park, Rochester, NY 14624, 

585–429–2264. 

Advanced Toxicology Network, 3560 

Air Center Cove, Suite 101, Memphis, 

TN 38118, 901–794–5770 / 888–290–

1150. 

Aegis Analytical Laboratories, Inc., 345 

Hill Ave., Nashville, TN 37210, 615–

255–2400. 

Baptist Medical Center-Toxicology 

Laboratory, 9601 I–630, Exit 7, Little 

Rock, AR 72205–7299, 501–202–2783 

(Formerly: Forensic Toxicology 

Laboratory Baptist Medical Center). 

Clinical Reference Lab, 8433 Quivira 

Road, Lenexa, KS 66215–2802, 800–

445–6917. 

Diagnostic Services, Inc., dba DSI, 

12700 Westlinks Drive, Fort Myers, 

FL 33913, 239–561–8200 / 800–735–

5416. 

Doctors Laboratory, Inc., 2906 Julia 

Drive, Valdosta, GA 31602, 229–671–

2281. 

DrugScan, Inc., P.O. Box 2969, 1119 

Mearns Road, Warminster, PA 18974, 

215–674–9310. 

Dynacare Kasper Medical Laboratories*, 

10150–102 St., Suite 200, Edmonton, 

Alberta, Canada T5J 5E2, 780–451–

3702 / 800–661–9876. 

ElSohly Laboratories, Inc., 5 Industrial 

Park Drive, Oxford, MS 38655, 662–

236–2609. 

Gamma-Dynacare Medical 

Laboratories*, A Division of the 

Gamma-Dynacare Laboratory 

Partnership, 245 Pall Mall Street, 

London, ONT, Canada N6A 1P4, 

519–679–1630. 

Kroll Laboratory Specialists, Inc. , 1111 

Newton St., Gretna, LA 70053, 504–

361–8989 / 800–433–3823 (Formerly: 

Laboratory Specialists, Inc.). 


sroberts on PROD1PC70 with NOTICES