Legislation

PDUFA Fact Sheet

Overview

• The Prescription Drug User Fee Act, or as it is commonly called, PDUFA, is the first of a series of laws that allow the agency to help fund the review of new drugs through fees paid by the companies that submit new drug applications. PDUFA was first enacted in 1992, and has been reauthorized twice, each time for five years, in 1997 and 2002.
• On September 30, the current PDUFA program will end. FDA has been working for over a year, in consultation with its stakeholders, to develop a new proposal for PDUFA reauthorization.
• The Agency has conducted meetings and consultations with all of FDA's stakeholders including Congress, industry, patient advocates and organizations representing health care professionals and consumers. The next iteration of the program will be known as PDUFA IV.

Proposed Recommendations

• To achieve the necessary public health benefits, the agency is seeking to increase total annual user fees to $392.8 million,^[1] an $87.4 million annual increase over the current base to:
  • Significantly broaden and upgrade FDA's postmarket safety system
  • Increase FDA's capacity to conduct advisory reviews of direct-to-consumer drug television advertising
  • Bring safe and effective new medications to the American public in a timely manner

Increases to Base User Fees

• $17.7 million to adjust the base amount for inflation and increases in salaries and benefits
• $11.7 million to cover a share of increased rents and the costs of the agency's required move to the new White Oak facility in Silver Spring, Maryland
• $20 million in additional fees to cover significant increases in FDA's drug review workload that were incurred but not compensated for under PDUFA III, and are expected to continue

Program Enhancements

• $29.3 million annually to be allocated to enhance the Agency's drug safety capabilities.
  • Increase in the number of FDA employees dedicated to safety evaluation of marketed medications.
  • Added resources to adopt new scientific approaches to drug safety, improve the utility of existing tools for the detection and prevention of adverse events, and incorporate them into our drug safety program
• $4.6 million annually to expedite and improve new drug development.
  • This includes development of new guidance to clarify requirements for new clinical trial designs, and work to clarify regulatory pathways in the areas of predictive toxicology, biomarker qualification and the handling of missing clinical trial data.
• $4 million annually to improve the information technology infrastructure for human drug review
  • This investment will help the agency to progress toward an all-electronic review environment
  • An all-electronic system would make our evaluation process more efficient, ease the identification of data inconsistencies and improve our use of clinical data submitted as part of new drug application to help monitor the overall safe and effective use of products once they are on the market.
• Establishment of a separate program to collect new fees from companies that seek FDA advisory reviews of their direct-to-consumer television commercials.
  • FDA anticipates that these fees will reach approximately $6.25 million a year and support 27 additional staff to carry out this function, and provide more timely reviews.

PDUFA Reauthorization Process

• Following today's posting of the PDUFA IV notice describing the proposals, FDA will present the proposals at a public meeting at the Grand Hyatt in downtown Washington DC. The meeting will be on February 16. Comments from that meeting and Federal Register notice will be evaluated and incorporated as appropriate in the final proposals that are submitted to Congress.
• PDUFA IV will go into effect only if it is enacted by Congress and signed by the President.

PDUFA History

• In 1992, Congress passed the Prescription Drug User Fee Act. The drugs user fee program was reauthorized by the Food and Drug Administration Modernization Act of 1997 and again by the Public Health Security and Bioterrorism Preparedness and Response Act of 2002.
• PDUFA authorized FDA to collect fees from companies that produce certain human drug and biological products. To market a new drug or biologic, a company must submit an application along with a fee. In addition, companies are assessed annual fees for each prescription drug product marketed and for each establishment that manufactures a product assessed a fee. Previously, taxpayers alone paid for product reviews through budgets provided by Congress. Under PDUFA, industry provides funding that is added to FDA's appropriated budget, and FDA commits to certain performance goals, which emphasize review timeliness as well as other performance measures.

PAST PDUFA GOALS

• PDUFA I
  • Review and act on a progressively increasing proportion of original NDAs, BLAs, and efficacy supplements within 12 months and resubmissions and manufacturing supplements within 6 months.
  • Review and act on 90 percent of priority NDAs, BLAs, and efficacy supplements (submissions that are for products providing significant therapeutic gains) submitted in FY 1997 within 6 months.
• PDFUA II
  • Review times were shortened and FDA met or exceeded nearly all its review goals
  • Expanded the scope of PDUFA work by including new goals intended to improve communication between FDA and application sponsors during the drug development process.
• PDUFA III
  • Review performance goals and the procedural and processing goals were largely the same as the PDUFAII FY 2002 performance levels for these goals.
  • Established several new initiatives to improve application submissions and FDA-sponsor interactions during drug development and application review.
  • Authorized FDA to spend user fee funds on certain aspects of postmarket risk management, including surveillance of products approved after October 1, 2002, for up to 3 years.

[1] All amounts will be adjusted annually for inflation and to reflect workload increases.

Source: FDA / PDUFA Fact Sheet

Abigail Alliance: Access, Compassion, Care, and Ethics for Seriously Ill Patients Act

The Parkinson Pipeline Project is supporting the Abigail Alliance for Better Access to Developmental Drugs in its initiative to make promising experimental treatments more readily available early in the drug development process. This applies to patients with life-threatening or chronically disabling diseases, who have exhausted all approved treatment options, including clinical trials, and compassionate and expanded use programs.

Aligned with the Pipeline Project’s underlying philosophy, the “Access, Compassion, Care, and Ethics for Seriously Ill Patients Act” seeks to:

• "Empower patients to choose their own treatment course by fully informing them of the risks and benefits of experimental medicines and ensuring they get counsel from their doctor."

A patient facing certain death is different from that of a patient with a non-terminal condition or remaining approved treatment options,” said Frank Burroughs, president of the Abigail Alliance. “When the risk of taking a less-well proven drug that might help an individual is weighed against the reality of certain death, allowing access to that drug is not only reasonable, it is their only chance.”

• Institute a “Tier 1” status for experimental treatments based on positive clinical evaluations of safety and efficacy as early as in Phase 1 testing. This supports the Pipeline Project’s view that a more effective approval process would stretch out the longer term study of new medicines into several smaller steps rather than the current single major step of “approval.”

“The need for certainty in drug approval is killing people,” Burroughs said. "Excessive caution is delaying the availability of potentially helpful treatments; slowing the absorption of new knowledge and diagnostic tools into medical practice; and discouraging the pursuit of vaccines and next-generation antibiotics that could save tens of millions of lives.

This “Deadly Caution” is the subject of an in-depth analysis of the role of FDA in making risk and benefit tradeoffs in development of the “miracles of scientific medicine” by award winning senior editor of Fortune, Clifton Leif.

Role of placebo in clinical trials

One provision in the ACCESS Act we would like to see softened calls for a ban on placebo-controlled trials in patients with life-threatening illnesses, challenging the ethics and efficacy of placebo-controlled studies as the “gold standard” for approval of new therapies. The Pipeline Project would ask the Abigail Alliance to refine the language to recognize the value as well as the limitations of placebo-controlled trials. We know that placebos are not always the best control group, and in the case of PD, the mechanism of the placebo effect (thought to result from release of dopamine in the brain as a result of expected benefits from the treatment), is directly confounded with the disease. When it comes to sham surgery, the placebo is a far cry from doing nothing.

The Abigail Alliance recently made headway when a Federal court upheld their case that terminally ill patients have a right to experimental treatments. Their lawsuit against FDA was sent back to the DC Circuit Court for a full hearing.

"Fortune" Magazine, "Deadly Caution," February 9, 2006

Advocates for Patient Rights Want Initial Approval for Unproven Drugs, Applied Clinical Trials, July 24, 2006

Read:  ACCESS Act S1956

Enzi-Kennedy Bill Would Give FDA Greater Authority Over Drug Safety, and Patients Greater Access to Most Current Research Data

The Senate is considering a bill (S3807) that “could drastically change” the Food and Drug Administration (FDA) testing and approval process by:

• Giving the agency greater authority to monitor the safety of new prescription drugs already on the market;
• Providing “better tools to identify, assess and manage risks post-approval.”
• Allowing patients and health care providers greater access to the most up-to-date clinical research data on which to base treatment decisions.1

The proposed Enhancing Drug Safety and Innovation Act of 2006 would establish a:

• Mandatory clinical trials registry for all late-stage trials, not just those that are experimental and for life-threatening diseases.
• Results database requiring inclusion of outcomes, and not just a list of ongoing clinical trials, as is the case with the existing ClinicalTrials.gov. 2

“The bill creates a framework for better pre-approval planning of how sponsors and the FDA will identify, assess and manage risks post-approval,” said Senator Edward Kennedy (D-Mass.) who, along with Senator Michael Enzi, introduced the bill in early August. “The result will be both a more efficient and effective way to obtain safety information, without … unduly delaying patient access to new therapies.”5

The bill also would “ensure that safety is not an afterthought, but a given,” and “restore public confidence in the FDA's process of reviewing the benefits and risks of prescription drugs,” said Enzi (R-Wyo.).1 Congress is not expected to act on this proposed legislation, however, until 2007 when the FDA Prescription Drug User Fee Act comes up for reauthorization, allowing for a raise in industry fees to cover the cost of increased oversight of prescription drug safety.

The Pipeline Project staff is currently evaluating the potential ramifications of the bill before lending its support.

Enzi-Kennedy Bill Provisions

Risk Evaluation and Mitigation Strategy (REMS)

• “Outlines a plan to improve post-market monitoring of drugs” by helping the FDA respond to risks identified after a product reaches market.2
• Requires the sponsor to develop and submit a risk evaluation and management strategy (REMS) before the FDA could approve a new drug or a new indication for an approved drug. This strategy would include periodic reports of adverse events, “a surveillance plan to assess known serious risks and to identify unexpected serious risks,"3 and “better communicate serious risks and side effects” to physicians and patients.” 2 The strategy would be reviewed at least annually for three years.
• Establishes a Drug Safety Oversight Board to help mediate any disputes that arise between the FDA and sponsors.

Reagan-Udall Institute for Applied Biomedical Research

• Establishes a public-private partnership at the FDA to “consider methods for more quickly assessing the safety of drugs to speed their path to the market.”3
• Creates new performance standards and predictive tools to provide faster and more certain answers about the safety and effectiveness of products in development. 2
• Identifies and coordinates research priorities between FDA regulators and researchers and distribute grants to fund these.

Clinical Trials Registry and Results Database

• Establishes a publicly available database at the NIH to encourage patient enrollment in and track progress of clinical drug trials.
• Requires registration of all late phase II, III, and IV clinical trials, and the posting of results — even negative ones.4
• Requires companies to deposit clinical trial data, along with technical and lay summaries, in a new, publicly available searchable database.4 Information would be submitted after a trial is cleared by the Institutional Review Board (IRB), but before patients enroll.
• Results would be submitted to the database after conclusion of data analysis. If regulatory action or publication is pending, the results would not be publicly available until that is resolved, protecting both commercially valuable trial results and the ability of researchers to publish their results.
• Audits would ensure that submitted results are “truthful, not misleading, and non-promotional.”

One weakness in the bill is the provision that would allow companies to delay making trial results public for up to two years while applying for marketing approval or trying to publish the data. “There needs to be the shortest amount of time possible between a trial ending and the data being made public,” says Sidney Wolfe, director of Public Citizen’s Health Research Group, a nonprofit watchdog.2 Industry representatives, however, claim that releasing clinical trial data may stifle innovation, even though the most sensitive business information—that on early-stage, exploratory trials—will remain in companies’ hands.2

Conflicts of Interest and FDA Advisory Committees

• Increases transparency and predictability in the FDA’s process for screening advisory committee members for potential financial conflicts of interest.
  • Requires the FDA seek qualified experts with minimal conflicts of interest, who are free of any financial ties to the companies affected by an issue before a committee, whenever possible.
  • If individuals without financial ties to such companies are not available, permits the FDA to grant waivers allowing  individuals with the necessary expertise to serve on the committee. However the agency must clarify how it made waiver decisions, and disclose those decisions at least 15 days before a committee meeting

Sources

1 Detailed summary of the Enhancing Drug Safety and Innovation Act of 2006 (7/17/06)
http://help.senate.gov/S___Bill Summary.pdf

2 Bouchie, Aaron.  Clinical trial data: to disclose or not? Nature Biotechnology. September 2006, 1058-60.
http:/www.nature.com/naturebiotechnology

3 Capitol Hill Watch|Sens. Enzi, Kennedy To Introduce Bill Giving FDA Greater Authority To Monitor Postmarket Safety of Rx Drugs
Kasier Network.org [Jul 20, 2006]
http://www.kaisernetwork.org/daily_reports/rep_index.cfm?hint=3&DR_ID=38610

4 Bouchie, Aaron. New drug safety bill in U.S. Senate. The Scientist. August 8, 2006.
http://www.the-scientist.com/news/display/24266/

5 The Enhancing Drug Safety and Innovation Act of 2006 Ted Kennedy.com
http://www.tedkennedy.com/content/1090/the-enhancing-drug-safety-and-innovation-act-of-2006

Medical News Today, June 10, 2006
Sens. Enzi, Kennedy To Introduce Bill To Overhaul How Medications Are Tested, Approved

S.3807 :
Title: A bill to amend the Public Health Service Act and the Federal Food, Drug, and Cosmetic Act to improve drug safety and oversight, and for other purposes. (Introduced August 3, 2006)
http://thomas.loc.gov/cgi-bin/bdquery/z?d109:s.03807:

New Rep. Phil Hare Honors Former Rep. Lane Evans During Stem Cell Debate

Statement from Representative Phil Hare on H.R. 3, the Stem Cell Research Enhancement Act of 2007:

I thank my colleague, Congresswoman DeGette for introducing the Stem cell Research Enhancement Act and for her strong leadership on this issue.

 

Mr. Speaker, last Thursday was a bitter-sweet day for me. I had the incredible honor of being sworn in as a new Member of Congress in front of my family, friends, and constituents. Yet part of me was sad that my friend and mentor, Congressman Lane Evans, wasn’t in my place. Lane served as a distinguished member of this body for 24 years until Parkinson’s disease forced him to retire at the end of the 109^th Congress.

Lane’s battle with Parkinson’s is testament to his incredible spirit that never caused him to ask, “Why me?,” although retiring meant he had to leave Congress when there was still so much he wanted to do to help veterans, working families and his constituents.

Mr. Speaker, Lane is just one of millions of Americans struggling with chronic illnesses that are curable with the advancement of stem cell research. Spencer House, the son of my good friend Doug, suffers from diabetes and must take four insulin shots everyday. Doug is encouraged by the hope that lies in embryonic stem cell research to offer his son a more normal life, and he is not alone. Poll after poll shows that the majority of Americans support ethical embryonic stem cell research as a way towards preventing others from having to live with illnesses like Parkinson’s, diabetes, cancer, Alzheimer’s, and spinal cord injuries.

I am an original cosponsor of this common-sense legislation because the science of stem cell research is clear: embryonic stem cell research has the potential to treat and cure some of our most debilitating injuries and diseases.

Mr. Speaker, today we decide whether to give the American people hope or continue to prolong the suffering of those who struggle with curable, chronic diseases. It’s time to put people above politics by providing millions of Americans with the hope of a better day and we will do that by passing this legislation. I urge all my colleagues to vote yes on H.R. 3. Thank you.

Parkinson's Action Network Applauds House Passage of Stem Cell Legislation

The Parkinson's Action Network (PAN) on Thursday applauded the House of Representatives for overwhelmingly passing legislation to expand embryonic stem cell research.

The legislation, H.R. 3, the Stem Cell Research Enhancement Act, passed by a bi-partisan vote of 253-174. The vote represents 15 more yes votes than during the 109^th Congress (H.R. 810).

PAN now turns to the Senate and asks that they pass S. 5, the Senate version of the same bill.

“The stronger support we see in this vote from last year solidifies what we already know: the majority of Americans are in favor of expanding scientific research,” said Amy L. Comstock, CEO, PAN. “On behalf of the Parkinson’s community, I would like to thank the House members who voted for this critical legislation. I now urge our Senators to pass S. 5 with great support.”

Prior to voting for HR 3, the House defeated a motion to recommit the bill which would have placed severe restrictions on institutions where somatic cell nuclear transfer research takes place. The motion to recommit fell by a vote of 189-238.

The legislation would expand current policy to allow federal dollars to be used for stem cell research on donated embryos from fertility clinic patients. This legislation also specifies strict ethical guidelines. The stem cells may only be derived from In Vitro Fertilization (IVF)-created embryos that would otherwise be discarded.

The current Administration policy states that federal funds may only be used for research on embryonic stem cell cultures created prior to August 9, 2001.

More than 120 million Americans suffer from chronic and life-threatening diseases, such as Parkinson’s disease, diabetes, cancer, heart disease, Alzheimer’s, Multiple Sclerosis, HIV/AIDS, ALS, osteoporosis and spinal cord injuries. Medical researchers have discovered that many diseases and injuries could potentially be treated or cured by new regenerative medicine therapies involving stem cells.

The Senate is expected to take up S. 5 in the coming weeks.

Source:  Parkinson's Action Network http://www.parkinsonsaction.org/content/view/288/10

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All rights reserved. Revised: 06/24/08.