Prescription Drug User Fee Act up for reauthorization

FDA sought input on fees, risk management issues

The Prescription Drug User Fee Act (PDUFA) program is once again up for renewal. Most pharmacy groups will stand behind the program — if a few changes are made.

"It has worked and should be reauthorized, although some improvements would be welcome," says Susan C. Winckler, RPh, JD, group director of policy and advocacy for the American Pharmaceutical Association in Washington, DC.

"It is a good thing to reauthorize. It certainly speeded up the drug approval process," says Gary C. Stein, PhD, director of federal regulatory affairs for the American Society of Health-System Pharmacists (ASHP) in Bethesda, MD.

In 1992, Congress passed PDUFA, which authorized the U.S. Food and Drug Administration (FDA) to collect fees from companies that produce certain human drug and biological products. Any time a company wants FDA to approve a new drug or biologic prior to marketing, it must submit an application along with a fee to support the review process. In addition, companies pay annual fees for each manufacturing establishment and for each prescription drug product marketed. In 1997, Congress passed the Food and Drug Administration Modernization Act, which included an extension of PDUFA until 2002 (PDUFA II). PDUFA II also expanded the number and type of performance goals that the agency would meet.

The legislative authority for the current PDUFA program, which has significantly reduced median drug approval time, will expire on Sept. 30, 2002. The president’s budget request for fiscal year (FY) 2003 recommends that PDUFA be reauthorized through FY2007. Tommy G. Thompson, secretary of the Department of Health and Human Services, announced the plan for PDUFA III March 13. The plan is now ready for consideration by Congress.

Before the plan was finalized, however, FDA asked for input on the current program from health professionals, patient groups, industry, and the general public. On Dec. 7, 2001, FDA held a public meeting to discuss reauthorization of PDUFA and to solicit stakeholder comments on future PDUFA provisions.

Many of the panelists at this meeting supported inclusion of post-market drug safety surveillance under PDUFA, an activity that currently is prohibited from user fee support. Some panelists also suggested that PDUFA cover increased FDA reviews of direct-to-consumer advertising.

Judy Cahill, CEBS, executive director of the Academy of Managed Care Pharmacy (AMCP) in Alexandria, VA, told FDA that post-marketing surveillance is an essential public health function of FDA because drugs have potential side effects, even when used appropriately. FDA, she said, is in the unique position to aggregate the drug data. She suggested that PDUFA impose a new user fee on manufacturers for the purpose of post-marketing surveillance and that FDA initiate a public awareness campaign aimed at encouraging the reporting of adverse drug events. Lastly, she suggested the possibility of an independent agency to conduct post-marketing surveillance activities.

ASHP also has expressed concern about post-marketing surveillance, Stein says. ASHP wrote FDA a letter on Jan. 25 as a follow-up to the December meeting. In the letter, ASHP strongly encouraged FDA to develop a comprehensive, proactive system for post-marketing surveillance of new drugs that is not dependent on volunteer reporting. This program, ASHP wrote, should include appropriate health professional and consumer education based on findings from the post-marketing surveillance system, and it should be funded through user fees.

The new plan takes note of these concerns, Thompson says. In a statement, he says the new proposal for the program has "significantly expanded resources for risk management activities related to medicines — especially after they enter the marketplace." Stein hasn’t seen the proposal, but says he has heard positive comments about changes in the post-marketing surveillance programs.

Avoiding a funding shortfall is another question facing the PDUFA program. Each year, the amount that FDA must spend from appropriations on the drug review process is increased by an inflation factor. Yet since 1992, FDA has not received increased appropriations to cover the costs of the across-the-board pay increases that must be given to all employees.

Also, the fees FDA has collected have been significantly less than expected due to the reduced number of new drug applications and the increased proportion of applications that are exempt from fees. Yet the number of goal-driven tasks for which FDA collects no fees has increased substantially under PDUFA II. "Congress has tended to not give full support to the [PDUFA] appropriations process," Winckler says. "[Congress] has been allowing the user fees to take the place of appropriations. That is not appropriate."

ASHP agrees. "PDUFA fees alone will not completely solve the problems in drug approval and review that are faced by FDA," it said in its letter to the agency. "Lack of appropriate congressional funding for other FDA programs compromises both review quality and drug safety."

Thompson says the funding issue has been tackled in the new proposal, as well. The plan "establishes a financial structure that should put the program on a sound footing for the foreseeable future."

Statistics about PDUFA

The Prescription Drug User Fee Act (PDUFA) program has produced significant benefits for public health, says Lester M. Crawford, DVM, PhD, deputy commissioner of the U.S. Food and Drug Administration (FDA). His remarks were made before the Subcommittee on Health, Committee on Energy and Commerce, U.S. House of Representatives, on March 6.

The median approval time for priority new drug and biologic applications dropped from 13 months in fiscal year (FY) 1993 to only six months in FY2000, he says. "We do not have complete data for FY2001, but median approval times are projected to remain at six months."

For standard new drug applications, the median approval time was 22 months in FY1993. By FY1999, however, median approval times had declined to 12 months.

During the PDUFA era, FDA reviewers have approved:

  • 30 new medicines for cancer;
  • 37 new medicines for AIDS;
  • 29 medicines to fight infection; and
  • 18 medicines for cardiovascular disease.

The pharmaceutical industry also enjoys significant research and development (R&D) savings, Crawford says, as a result of shorter review times. "Each month of reduced review results in an average savings of $2.5 million, or $30 million in R&D cost savings over 12 months. Given that FDA approves an average of 40 NMEs [new molecular entities] and biologics per year, the savings to industry represent $1.2 billion annually. The program represents a bargain in light of the $133 million that industry paid in user fees in FY2001."

Finally, he says, PDUFA also has brought significant benefits for FDA:

  • Performance goals have helped streamline and harmonize the management of drug and biological product reviews.
  • The program’s requirement for comprehensive product reviews and responses has resulted in improvements to the quality of the application review process.

"Most importantly, the fees have enabled the agency to hire additional medical reviewers and other specialists, and upgrade the technology that is essential for the success of the program," says Crawford.

Some critics have argued that speeding up the approval process through PDUFA increases the likelihood that drugs will be pulled off the market. Susan C. Winckler, RPh, JD, group director of policy and advocacy for the American Pharmaceutical Association in Washington, DC, disagrees. "The withdrawal of drugs from the market is statistically about the same from before PDUFA to after PDUFA."

That’s correct, according to statistics provided by FDA. Before the user fee program passed in the PDUFA, the withdrawal rate was 2.7%. The rate for drugs reviewed under PDUFA (since 1994) is still 2.7%, even though approval times are now about 12 months, compared to 30 months before PDUFA.

Still, Crawford acknowledges in his testimony the risk of bringing new drugs to market that have been tested on a limited population size. "While drugs and biological products are under development, clinical testing is usually limited to small, carefully selected populations of 5,000 or less. After approval, however, millions of patients may be exposed to the drug.

"However, the need to institute a more effective program of risk management for new drugs, and thereby ensure greater patient safety, is clearly warranted by the intrinsic limitations of drug development programs (particularly the size of clinical trials) and the reality that more drugs are launched for the first time in the United States."