The Prescription Drug User Fee Act (PDUFA) was a law passed by the United States Congress in1992 which allowed the Food and Drug Administration (FDA) to collect fees from drug manufacturers to fund the new drug approval process. PDUFA has had a significant role in modern drug review at FDA. Before PDUFA, FDA's review process was understaffed, unpredictable and slow. FDA lacked sufficient staff to perform timely reviews or develop procedures and standards to make the process more rigorous, consistent, and predictable. FDA lacked the funds to provide computers to all FDA reviewers.

1. PRESCRIPTION DRUG USER FEE ACT (PDUFA)
INTRODUCTION
The Prescription Drug User Fee Act (PDUFA) program is the cornerstone of modern FDA drug
review. PDUFA review and approval of new drug applications, while keeping FDA's high
standards.
The Prescription Drug User Fee Act (PDUFA) was a law passed by the United States Congress
in1992 which allowed the Food and Drug Administration (FDA) to collect fees from drug
manufacturers to fund the new drug approval process. FDA was entitled to collect a substantial
application fee from drug maker at the time a New Drug Application (NDA) or Biologic's
License Application (BLA) was submitted, with those funds designated for use only in Center
for Drug Evaluation and Research (CDER) or Center for Biologic's valuation and Research
(CBER) drug approval activities. In order to continue collecting such fees, the FDA is required
to meet certain performance benchmarks, primarily related to the speed of certain activities
within the NDA review process.
IMPLEMENTATION OF PDUFA
The move towards imposing user fees to pay for the regulatory review of new medicines was
the result of dissatisfaction among consumers, industry, and the FDA. The FDA estimated
that a delay of one month in a review’s completion cost its
sponsor $10 million. The FDA argued that it needed additional
staff to end its back-log of drugs awaiting approval for market.
PassedtheSenateonOctober7, 1992 (passed voice vote) Signed
into law by President George H.W. Bush on October 29, 1992.
PDUFA has had a significant role in modern drug review at
FDA. It has been a key to ending major problems with
unpredictable and slow review and approval of new drug
applications. It has provided funds to eliminate or even reverse
so called "drug lag" attributed to inadequate staff and computer
resources. Americans now get access to more new medicines
faster than patients in other countries, while prior to PDUFA, American patients waited for
FDA to act long after new drugs were available in Europe.

2. Major Factors Resulting in Enactment of PDUFA in 1992
Drug review at FDA prior to PDUFA entailed a variety of problems that PDUFA alleviated.
Before PDUFA, FDA's review process was understaffed, unpredictable and slow. FDA lacked
sufficient staff to perform timely reviews, or develop procedures and standards to make the
process more rigorous, consistent and predictable. FDA lacked the funds to provide computers to
all FDA reviewers. Simultaneously, regulators in other countries were able to review products
faster. Access to new medicines for U.S. patients lagged behind. For example, U.S. patients
were not getting access to new AIDS drugs as quickly as in other countries. Chronic
understanding of drug review and related delays in U.S. patient access to new drugs led to the
1992 enactment of PDUFA.
PDUFA was established to increase FDA funding for human drug review and to increase the
speed and predictability of the review process. Under PDUFA the U.S. pharmaceutical and
biotechnology industries would pay user fees and FDA would commit to develop a more
standardized process and faster, more predictable review time frames. 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 up the application review process for new
drugs and biological products without compromising FDA's high standards for approval.
Since the beginning of the program, there has been a significant improvement in FDA funding
for the drug review program, including significant investments in information technology.
PDUFA has enabled the nominal funding for human drug review to increase by over 225 % from
1992 to 2004. Because Congressional appropriations have grown at a much lower rate, user fees
now represent over half of all resources devoted to the review of human drugs.
BOARD MEETINGS AT CLINICAL TRAILS

3. Scope and Importance of PDUFA - Supported Work
The activities encompassed in the PDUFA "process of human drug review," that are needed
to improve drug development and speed patient access, begin well before a product sponsor
submits a new drug application for FDA pre--market review. Although not often discussed,
these other FDA labour intensive activities are critical to improving the quality of a sponsor's
drug development and the quality of a submitted market application. High quality
development is crucial to patient safety during clinical trials and to ultimate approval of a
safe and effective product. Application quality is a decisive factor in drug review and
approval.
The evolution of PDUFA
The length of the drug approval process fell under severe scrutiny during the early years of the
AIDS epidemic. In the late 1980s, ACT-UP and other HIV activist organizations accused the
FDA of unnecessarily delaying the approval of medications to fight HIV and opportunistic
infections, and staged large protests, such as a confrontational October 11, 1988 action at the
FDA headquarters which resulted in roughly 180 arrests. In August 1990, Louis Lasagna, then
chairperson of a presidential advisory panel on drug approval, estimated that thousands of lives
were lost each year due to delays in approval and marketing of drugs for cancer and AIDS.
Partly in response to these criticisms, the FDA introduced expedited approval of drugs for life-
threatening diseases and expanded pre--approval access to drugs for patients with limited
treatment options. All of the initial drugs approved for the treatment of HIV/AIDS were
approved through accelerated approval mechanisms. For example, a "treatment IND" was
issued for the first HIV drug, Zidovudine, in 1985, and approval was granted 2 years later,
in1987.
AIDS activists, desperate for new treatments, were outraged at the cost of those first drugs
and the slow pace of drug development. These activists bombarded the government and drug
companies with complaints and public protests. The activists won a major victory in 1989,
when Burroughs Wellcome implemented a 20% price cut on Zidovudine, then still the only
treatment for HIV. Even after this price concession, the 12-pill-per-day Zidovudine regimen
cost patients $6,400 a year. AIDS activists expressed their anger by trashing booths at medical
conventions and continuing local public protests. Gradually, drug companies established
relationships with AIDS activists and the two sides came together to improve clinical trials.
By August 1991, relations had warmed up so much that ACT- UP founder Larry Kramer
wrote Bristol - Myers Squibb chief Richard Gelb a letter of congratulations on the imminent
approval of Videx. AIDS groups fought for the re-authorization of the Orphan Drug Act and
the passage of the Prescription Drug User Fee Act in 1992.
Background on the Act
The Prescription Drug User Fee Act of 1992 created the biggest and most important changes
at the FDA over the past generation. The legislation permits the FDA to charge a fee to a drug
sponsor who submits a new drug application. The fees allowed the FDA to increase its NDA

4. review staff by 50%. It was hoped that with more staff the agency could approve NDAs faster
and therefore reduce the drug lag problem. Before passage, average NDA approval times had
ballooned to over two years, even though the Kefauver-Harris amendments had envisioned
that the approval of the NDA should only require 180 days for the approval.
PDUFA I
The Prescription Drug User Fee Act (PDUFA) was first enacted in 1992. PDUFA gives the Food
and Drug Administration (FDA) a revenue source, fees paid by pharmaceutical companies
seeking the approval of new drugs, to supplement but not replace direct appropriations from
Congress. PDUFA was passed in order to shorten the length of time from a manufacturer’s
submission of a New Drug Application or a biologic's license application to FDA decision
approval or license.
Congress created three kinds of user fees via PDUFA and required that they each make up one
third of the total fees collected. These include application review fees paid by the sponsor for
each drug or biologic application submitted, establishment fees paid by manufacturers annually
for each of its facilities, and product fees paid annually for each product on the market covered
by PDUFA. The law provided exemptions and waivers for applications from small businesses,
drugs aimed at orphan diseases, or unmet public health needs.
PDUFA II
In its 1997 re-authorization of PDUFA, Congress enacted stricter performance goals, required
increased transparency in the drug review process, and tried to facilitate better communication
between drug makers and patient advocacy groups. Congress expanded the scope of the law
making to include the investigation phases of a new drug’s development. PDUFA II was passed
as Title I of the Food and Drug Administration Modernization Act. When Congress was debating
the legislation that implemented PDUFA II.
PDUFAIII
PDUFA III, part of the Public Health and Bio terrorism Preparedness Act, made
appropriations for increased post - market monitoring of new products and allowed the FDA
to hire additional personnel to speed the reviews of new drugs. Another 2002 statute extended
user fee policies to cover the approval process for medical devices. During the period that
PDUFA III was in effect the FDA's requirement that drug companies pay user fees
for505(b)(2) applications to switch drugs from requiring a prescription to being sold over -
the - counter became a source of controversy.
PDUFA IV
The FDA requested and received fees inclined to cover increased review workload and expanded
post marketing safety initiatives, as well as the authority to apply user fees to the monitoring of

5. direct to consumer drug advertising. President Bush signed the re-authorization of PDUFA into
law on 27 September 2007.
PDUFA V
The re-authorization process for PDUFA V began with a public hearing in April 2010. PDUFA
was reauthorized in July 2012.The Pharmaceutical Research and Manufacturers of America
(PhRMA) strongly supported re-authorization of PDUFA, saying at the time that “PDUFA V
can play a critical role in making more life-saving medicines available to patients in a timely
manner, strengthening the scientific base of the FDA and providing a steady, reliable stream of
resources for Agency scientists."PDUFA's fifth re-authorization calls for upgrading
benefit/risk assessments of new medicines as well as calling for more patient perspectives in
the review process.
TYPES OF PRESCRIPTION DRUG USER FEE ACT
Effectiveness
Increased staffing
A 2002 U.S. Government Accountability Office (GAO) report found that PDUFA funds allowed
the FDA to increase the number of new drug reviewers by 77% for first eight years of the act.
The minimum approval time for no priority new drugs dropped from 27 months to 14 months
over the same period.

6. Drug launches
Faster drug approval times and other PDUFA - related changes have led to pharmaceutical
companies targeting more drugs for first launch in the United States thus increasing patient
access to new medicines. Faster drug review from 1990 to 2001 was found to increase the
probability of a drug being launched first in the United States by 14%. Other changes made
under PDUFA such as the increased probability of approval and shortened development periods
increased the probability of a drug being first launched in the United States by 31% at the end of
PDUFA I and 27% at the end of PDUFA II. During the eight years before PDUFA took effect, an
average of 24 new drugs were approved each year. The number of approvals ranged from 20 in
1988 to 30 in 1991. During the four years that PDUFA I was in effect, an average of 32 drugs
were approved each year, ranging from 22 in 1994 to 53 in 1996. The average number of new
drugs approved by the FDA each year increased by one - third. First drug launches using new
chemical entities in the United States increased from 44 from 1982 through 1992 to 156 in 1993
through the 2003 period. The increase in first drug launches in the United States from 1993
through 2003 is particularly interesting given that the European Union harmonized its regulatory
regime for new drugs with those of other major markets in order to reduce barriers for drug
approvals during the same period.
Role of Regulatory Industry
It is described improved communication between the FDA and the drug industry on what data
should be included in NDAs as an important benefit of PDUFA. In fiscal year 1993, 34 of the
new applications that came into the FDA were sent back to the company because they were
poorly prepared or missing critical information. In fiscal year 1996 six applications were refused
due to poor regulatory documentation.
FDA scale of fees in the approval process
FDA calculates the fees for the following year based on the expected work (applications
etc.) and the amount it wants to raise from the fees. For 2008 the application fees are:
 $1,178,000 per full application requiring clinical data
 $589,000 per application not requiring clinical data or per supplement requiring clinical
data.
 Establishment fees and product fees.
The FDA budget due user fees imposed under PDUFA is expected to add $707 million to the
FDA budget in 2011, roughly a quarter of the agency's total spending. User fees cover roughly
65 % of the drug approval process.
Recent Amendments of PDFUA
The U.S. Food and Drug Administration (FDA) initiated the PDUFA re-verify process through a
public meeting on July 15, 2015. For more than 20 years, since enactment by Congress in 1992,

7. PDUFA has helped provide patients with more timely access to innovative, safe and effective
medicines to combat diseases, such as cancer, cardiovascular disease, infectious diseases and
more. PDUFA provides FDA with necessary resources to meet performance goals for the
regulatory review of new medicines.
Here are some key dates:
October 1, 2012 : PDUFA V (most recent PDUFA) enacted
September 15, 2015 : FDA/Industry technical negotiations for PDUFA VI commence
September 30, 2017 : PDUFA V expires
For more than 20 years, PDUFA has helped the FDA fulfil its central mission – to protect and
promote the public health by allowing the Agency to keep pace with the rapid increase in the
number and complexity of innovative drugs and biologic's entering the drug development and
regulatory review pipeline. The PDUFA program has enabled FDA to hire additional staff to
review applications for new drugs and biologic's. In 1989, FDA’s Human Drug Review Program
was staffed by approximately 1,900 employees – by 2014, the human drug review staff had
grown to more than 3,700.
How it works
Bio-pharmaceutical companies pay three different user fees under PDUFA:
Application fees: Fee due when a sponsor submits a New Drug Application (NDA) or Biologic's
License Application (BLA).
Product fees: Annual fees for marketed drugs for which no generic versions are approved.
Establishment fees: Annual fees for each manufacturing site that manufactures at least on
approved prescription drug for which no generic versions are approved.
Re-authorization of PDUFA
Re-authorization of PDUFA is critical to ensuring America’s bio-pharmaceutical companies can
continue scientific innovation and bring new treatments to help patients live longer, healthier
lives.

8. Re-authorization timeline
Re-authorization of Prescription Drug User Fee Act
Positive Aspects of PDUFA
More predictable and streamlined process.
Reduce approval and review times.
The user fees are the added resources for the more review staff.
Enhancement of drug development through periodical meeting in collaboration
with the industries.
Speed up the FDA approval process for the new drugs.

9. REFERENCES
1. http://www.fda.gov/ForIndustry/UserFees/PrescriptionDrugUserFee/ucm119253.htm
2. https://en.wikipedia.org/wiki/Prescription_Drug_User_Fee_Act
3. http://www.wsj.com/articles/sarepta-fdas-decision-on-dystrophy-drug-delayed-
1464181087
4. http://www.nber.org/papers/w10822
5. https://dash.harvard.edu/bitstream/handle/1/8889473/Wheeler_Alusheyi.pdf?sequence=1
6. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3541836/