Healthy Skepticism Library item: 17917

Warning: This library includes all items relevant to health product marketing that we are aware of regardless of quality. Often we do not agree with all or part of the contents.

Publication type: Legal Rule/Regulatio

Background on the Prescription Drug User Fee Act
Patient and Consumer Coalition 2002 Mar

Full text:

The Prescription Drug User Fee Act was enacted in 1992 to address concerns about the length of time it took for new drugs treating life-threatening and disabling conditions-especially AIDS— to be reviewed and approved by the FDA. The authors of PDUFA recognized that Congress was not going to provide enough in new appropriations to support the increased staff that a shorter approval process would require. PDUFA mandated that drug manufacturers pay user fees when they filed a New Drug Application for review and approval of a product.

PDUFA was reauthorized in 1997 as part of the Food and Drug Administration Modernization Act. However, this iteration included more stringent “performance goals” requiring that the FDA meet very tight review deadlines. These faster deadlines were insisted upon by the pharmaceutical industry, which argued that these “measurables” were necessary to ensure that the user fees they paid were not dispersed to fund other agency activities. For the first time, PDUFA II also included stipulated time frames for the scheduling of meetings and response to industry requests (“management goals”).
As a result of PDUFA I and II, the FDA has both dramatically increased the amount of resources it devotes to new drug and biologics review and decreased the review time. But this has come at a price. PDUFA requires that the agency increase funding from non-user fee revenues for drug reviews by an inflation-adjusted amount every year. But, Congressional appropriations for the FDA have not kept pace with inflation and with the increased mandates on and responsibilities of the agency. As a result, the only way the FDA can comply with PDUFA’s requirements to increase non-user fee funding for the drug review process is to take resources away from other essential activities, such as post-market research and surveillance, on-site inspections, and regulation of medical devices. Moreover, the agency has said that user fees generate less than the total expenditures the agency must make to satisfy PDUFA performance and management goals. As Former Commissioner Jane Henney said, “…the truth is, the program is barely surviving because of the way it was designed. We don’t have the resources to do the things we believe are essential, such as adverse event reporting, because they are not supported by PDUFA funds.”[i]

The short review times mandated under PDUFA II have had other negative effects. The director of FDA’s Center for Drug Evaluation and Research, Dr. Janet Woodcock, has expressed a great deal of concern about the high rate of turnover among review staff, which means that the agency has had difficulty retaining experienced, competent reviewers. Dr. Woodcock has said that the intense timelines under PDUFA have created a “sweatshop environment that’s causing high staffing turnover.”[ii]

There have also been concerns about a series of high-profile drug withdrawals over the last few years. According to the Pulitzer Prize-winning investigation by David Willman of the Los Angeles Times, seven of these drugs— Lotronex, Propulsid, Rezulin, Raxar, Posicor, Duract and Redux—are suspected in 1,002 deaths.[iii] While FDA officials claim that these safety problems were not necessarily linked to PDUFA, the withdrawals raise troubling questions about whether the agency performance goals mandated by the Act may be overriding its public health responsibilities.

In fact, several former FDA employees told the Los Angeles Times that they were under a great deal of pressure to approve drugs quickly. Bill Schultz, former deputy commissioner at the FDA said, “You can meet the [performance] goal by either approving the drug or denying the approval. But there are some who argue that what Congress really wanted was not just decisions, but approvals. That is what gets dangerous.” Dr. Solomon Sobel, the former director of the FDA’s metabolic and endocrine drugs division told the Los Angeles Times that deadline pressure under PDUFA was not just to make decisions: “The pressure to meet deadlines is enormous. The basic message is to approve.”[iv]

Reauthorization of the Prescription Drug User Fee Act
The undersigned members of the Patient and Consumer Coalition believe that the upcoming re-authorization of PDUFA offers an important opportunity to increase the safety of prescription drugs and devices in this country and to insure that the protection of the public’s health is the FDA’s top priority under the Act. We urge Congress to:

q Hold balanced hearings on PDUFA reauthorization and drug safety concerns. The hearings should include testimony from patients who have been harmed by problem drugs-or their representatives-and consumer advocates who are knowledgeable about PDUFA. Such hearings would send a vital signal to FDA from Congress that what the public wants and deserves is a thorough review and oversight process for drugs and biologics, not just speedy approval of new products.

q Adequately fund the entire range of FDA’s approval and safety oversight activities from general revenues. There is an urgent need for increased funding for post-marketing surveillance and other safety-related activities not covered by current user fees. User fees are not a substitute for adequate federal funding of these vital and growing public health functions. Adherence to this principle would be the surest way to remove the worrisome potential for conflict-of-interest that arises when dedicated income streams flow to the regulator from the regulated industry.

q Give the FDA total control over all review and surveillance activities. If an unwillingness to appropriate adequate funds leads Congress to consider the expansion of user fees, it is absolutely essential that the FDA alone determine their usage, without the kind of inappropriate control over the use of these fees (through mandated decision-making deadlines) that the industry has exercised with new drug approvals.

q Address drug safety concerns created by PDUFA’s excessive and inappropriate focus on swift approval over public health. PDUFA III should include new safety protections that, to the greatest extent possible, protect the public from potential harm caused by adverse reactions, side effects and adverse events related to pharmaceutical products and biologics. Decision-making deadlines for drug review should be redefined to focus on the FDA’s responsibility to guarantee safe drugs, not only on the speed with which reviews are conducted. The agency’s antiquated and under-funded adverse event reporting system (for drugs, biologics and devices) should also be modernized.

1. RESTRUCTURE USER FEES

q Eliminate the linkage between appropriated and user fee funds. The current law results in disproportionate funding for the drug approval process compared to most other research, regulatory, and public education functions. At a minimum, the program must be re-designed in such a way as to prevent the draining of funds from vital FDA functions.

q Require that user fees support the life cycle of the review process. Presently, FDA staff hold numerous pre-New Drug Application meetings with manufacturers before the agency receives any PDUFA fees for the intended application. While these meetings benefit sponsors greatly by improving their understanding of FDA expectations and the quality of their applications, they also divert FDA staff time from other review functions and increase the cost and difficulty of meeting PDUFA goals. In other words, the required meetings are an un-funded mandate on the agency.

2. ELIMINATE OR OVERHAUL PERFORMANCE GOALS

Although PDUFA’s deadlines are for decision-making on drugs and biologics, not approval, these goals put the FDA under tremendous financial pressure to move very quickly on the overall approval process. By requiring that decisions must be made within the same timeframes for priority and standard reviews,[v] these goals force the agency to take an unvarying, “cookie cutter” approach to approvals. Congress should eliminate these required goals. If this does not occur, the agency should be given greater flexibility to set its own priorities and/or extend the goals, including:

q Consult All Stakeholders – If performance goals are not eliminated in PDUFA III, consumers and patient representatives should be involved in developing them.

q Grant FDA a “Scientific Override” – When the FDA requires additional information or clarification from the manufacturer as part of the review process, the FDA should be allowed to “stop the clock” on review deadlines while waiting for this information to be provided.

q Eliminate Rigid Management Goals — These goals require the agency to set up meetings with the industry within specific timeframes. They should be replaced by a more flexible system that allows the FDA to prioritize these requests, thus decreasing undue burden on the agency.

q Allow FDA More Flexibility For Standard Reviews –There is no public health justification for requiring the FDA to decide on a “me too” drug that duplicates therapies already on the market at the same speed as a drug that might offer therapeutic advantages to some patients. The FDA should be granted greater authority to prioritize the review of standard drug applications.

q Create Safety Goals – FDA should establish performance goals oriented toward protecting the health and welfare of consumers, such as tracking and reviewing Phase IV trials, improving the collection, analysis and response of adverse event reports, and enhancing the speed and quality of review of direct-to-consumer advertisements.

3. ENHANCE DRUG SAFETY MEASURES AND FDA ENFORCEMENT AUTHORITY

q Grant FDA Civil Monetary Fine Authority and Subpoena Power – When companies fail to complete Phase IV confirmatory trials or when companies repeatedly violate prescriber and direct-to-consumer advertising guidelines, the agency should be given the authority to levy significant monetary penalties.[vi] The agency should also have the power to compel companies to produce relevant documents.[vii]

q Launch Independent Drug Withdrawal Investigations — An office or agency independent of the FDA should investigate the circumstances surrounding the withdrawal of medical products from the market, as the National Transportation Safety Board does for plane crashes.

q Increase Monitoring and Review of Phase IV Trials – Require the FDA to track Phase IV trials, strictly monitor and enforce the informed consent and protection of human subjects in those studies, and, in a timely manner, review the quality of the studies and the accuracy of the findings.

q Improve Adverse Event Reporting – Hospitals, HMOs, nursing homes and other healthcare providers should be required to automatically report (the present system is voluntary) serious adverse drug events, adverse reactions and medical errors to the FDA, CDC, and/or other relevant agencies. Appropriations for FDA’s oversight of adverse event reporting should be dramatically increased.

q Utilize the Centers for Education and Research on Therapeutics – CERTS should examine the feasibility of: (1) implementing a patient self-monitoring reporting system for signaling possible adverse drug reactions;[viii] and, (2) expanding the use of medical registries to follow patients who may be at risk of serious reactions

q Broaden Distribution of Medication Guides – Consumers should be given power to make informed decisions about drugs and devices and to avoid preventable harm. It is time to mandate that medication guides with scientifically accurate, unbiased and clearly worded information about the risks and benefits of a treatment be included with every dispensed drug (as proposed by the FDA in 1995.) Such medication guides would also, for the first time, provide a mechanism for notifying consumers directly when new safety concerns about a drug emerge that require a change in a drug’s approved labeling.

q Provide Consumers with More Post-Market Drug Safety Information — Section 506B of the Food, Drug and Cosmetics Act should be amended to expand the scope of information made available to the public to include information as study protocols, patient accrual rates, reports of unexpected, i.e., unlabeled, suspected adverse reactions, and study results.[ix]

q Scrutinize Single Controlled Clinical Studies – An increasing number of drug manufacturers have indicated that they will begin submitting new drug applications using data from only one controlled clinical study, which is now allowed by law, rather than multiple studies. An independent study should be conducted at an appropriate time to assess the effectiveness of single controlled studies in assessing the safety of drugs and biologics.

q Examine Comparative Safety Data – Manufacturers should be required, as part of their application to the FDA to market a new drug or biologic, to submit the results of tests comparing the safety and efficacy of their product to others already on the market that are used to treat the same indication.

This position paper is endorsed by the following members of the Patient and Consumer Coalition: the Alpha-1 Foundation; Center for Medical Consumers; Consumer Federation of America; Gray Panthers; International Union, UAW; the National Consumers League; the National Organization for Rare Disorders; the National Center for Policy Research for Women & Families; the National Women’s Health Network; and the Title II Community AIDS National Network.

[i] FDA Consumer Magazine, “User Fees for Faster Drug Review: Are They Helping or Hurting the Public Health?,” September-October 2000.

[ii] Ibid.

[iii] David Willman, “How a New Policy Led to Seven Deadly Drugs,” Los Angeles Times, December 20, 2000.

[iv] Ibid.

[v] PDUFA II establishes deadlines that require FDA to review 90 percent of priority (“fast track”) new drug applications within 180 days and 90 of standard applications within ten months.

[vi] As a condition of approval of a new drug by the agency, drug companies often commit to doing post-marketing or Phase IV studies. These studies can help to identify previously unknown dangers presented by a new drug so that its safety labeling can be updated or if necessary the drug can be withdrawn. According to a Public Citizen report released in 2000, of the 88 new drugs that were approved between 1990 and 1994 with the understanding that the sponsor would complete at least one post-marketing study, only 13 percent (11 of 88) had completed all of the studies they had agreed to as of December 1999.

[vii] According to a 1990 Congressional Research Service study, almost every other U.S. health and safety regulatory agency has subpoena power. Without the ability to subpoena company records, the FDA’s efforts to assure drug safety are hamstrung. The case of the FDA’s post-approval investigation of the drug Halcion demonstrates the problems the agency faces. In that case, the agency could not subpoena the company’s records even though it had suspicions of criminal wrongdoing. At one point in that investigation, the agency even went so far as to ask for the intervention of a federal judge to modify a gag order in a tort action against the maker of Halcion so that the agency could have access to crucial documents.

[viii] Under this system, suggested by Seymour Fisher and Stephen G. Bryant, patients would be given information about how to report adverse drug reactions by their pharmacist. This system would make it possible to compare the rates of adverse drug reactions to a new drug with drugs already on the market for the same indication. , (S. Fisher, S.G. Bryant, “Postmarketing surveillance of adverse drug reactions: patient self-monitoring,” Journal of the American Board of Family Practice, 1992; 5:17-25.)

[ix] Under its proposed rule of December 1999 implementing FDAMA’s requirement for the industry to report its progress on completion of phase IV tests to the agency this information would have been made available to the public. However the industry objected, claiming that FDAMA did not give the agency the authority to make this information public and this requirement was removed from the final rule, which was published in October of 2000. Legislation is needed to clearly give the agency the authority it needs to disclose this information.