Reauthorization of the Prescription Drug User Fee Act

Mr. Chairman and Members of the Subcommittee, I am Mary K. Pendergast, Executive Vice President for Government Affairs at Elan Pharmaceuticals Management Corporation. I am pleased to be here today on behalf of the Biotechnology Industry Organization (BIO), to talk with you about the Prescription Drug User Fee Program and to urge the Subcommittee and the Congress to reauthorize this program, which expires at the end of this fiscal year.

The Biotechnology Industry Organization, BIO, represents more than 1000 biotechnology companies, academic institutions, and state biotechnology centers in all 50 U.S. States. BIO members are involved in the research and development of health-care, agricultural, and environmental biotechnology products. The companies BIO represents range from large, multinational corporations to much smaller, emerging companies. Since its establishment in 1993, BIO has worked with this Subcommittee on a variety of issues, including the one we discuss today -the product review and approval process at the Food and Drug Administration (FDA). BIO was active during congressional deliberations in 1996 and 1997 that led to the Food and Drug Administration Modernization Act and, importantly, to the reauthorization of the Prescription Drug User Fee Act (PDUFA).

I want to begin by thanking this Subcommittee and its Members for your work over nearly ten years in creating and then continuing the user fee program for drugs and biologics. You were there at the beginning, with the first user fee bill sponsored by Mr. Dingell, Mr. Waxman, and others on the Energy and Commerce Committee; you were there five years later at the first reauthorization, with legislation sponsored by you, Mr. Chairman, Mr. Burr, Mr. Greenwood, and others; and here you are again. We greatly appreciate your support of this critical program.

I also want to reiterate what already has been said here today: the Prescription Drug User Fee Act has been and remains an extraordinarily successful piece of legislation. Prior to enactment of PDUFA, FDA was often behind other nations of the world in approving new pharmaceutical products. What Congress and FDA repeatedly heard was that American patients waited while patients elsewhere had access to important new therapies. The drug and biologic user fee program reversed that scenario. Because of the additional funding made possible through the user fee program, the United States now leads the world, rather than following it. Today, FDA is the world's leading regulatory agency, not only in terms of the quality and safety of the products it approves for marketing, but also in terms of ensuring that new products are available to patients as soon as possible.

For BIO, two key measures of the success of PDUFA I were, first, whether the law has facilitated FDA's review and approval of new products without compromising the agency's ability to make sound scientific, medical, and regulatory decisions and, second, whether the law worked for patients.

By both of these measures, the initial user fee program succeeded. User fees enhanced FDA's resources so the agency could hire additional medical and scientific reviewers and function more effectively in its review of new products. And that was accomplished without a diminution in safety. Anyone who has worked with FDA knows they are now, as they always have been, the toughest regulators in the world. User fees have not changed that, nor has reducing average review times changed the proportion of products withdrawn from the market for safety reasons.

Thus, when the time came to reauthorize the program in 1997, there was a keen recognition that we were seeing something unusual - a newly established program that had worked the way it was expected to work - one that a wide variety of stakeholders were praising. PDUFA II also has been successful by many measures. Communication between FDA and application sponsors has continued to improve, leading to better applications and more effective use of scientific resources in making decisions. And, most importantly, the health of patients has improved through access to new products like Herceptin for metastatic breast cancer, Zevalin for non-Hodgkins lymphoma, Enbrel - the first disease modifying agent for rheumatoid arthritis, Xigris - the first therapy for life-threatening sepsis, and Synagis to protect newborns from potentially fatal infections.

Mr. Chairman, as the Subcommittee moves forward with its work on reauthorizing this program for a second time, we know you will build on its successes. In particular, we are hopeful that in the next five years of the user fee program, while FDA maintains the strong standards it now requires, we will see enhanced efforts regarding product safety. This enhanced product safety program - FDA's risk management proposal - will be supported by user fees. With these additional user fees, FDA's risk management program will hopefully prove to be an even better pharmacovigilance system than that which already exists in the United States.

We also hope that you will recognize that positive results do not necessarily equate with perfection. As we have looked more deeply into the statistics regarding what has occurred over the last four years, we have recognized that some modifications in how the program is implemented may be in order and may improve on successes already achieved. The things we are looking at do not involve ways in which we think the law needs to be changed. Indeed, it is BIO's view that minor, largely technical, changes in the law may be called for, but that fundamentally this statute works well and should remain essentially intact. We also hope that this important legislation will not become a magnet or a train to which many unrelated provisions will be attached.

Reports of PDUFA progress generally deal in averages across the agency, and often do not separate these averages to allow examination of whether different components of the agency are fulfilling the goals of PDUFA at the same level. This kind of sub-analysis is of great importance to the biotechnology industry, which often brings to FDA products that are complex, unique, and the outgrowth of emerging science. We are keenly interested in how the process for reviewing these biotechnology products - which are the primary preserve of the Center for Biologics Evaluation and Research (CBER) - and the time frames in which they are reviewed, tracks the review process and time frames for other pharmaceutical products.

When BIO has examined the data, we have seen what appear to be significant differences among review divisions, as well as from one center to another, in both the review processes and the time frames for application reviews. We want to understand the reasons for these differences and we want to find ways to address and even reduce or eliminate them.

To achieve this goal, BIO is proposing some modifications that we hope will enhance the FDA's review processes over the next five years. These proposals would not require any change in the legislation, nor in the standards for approval, but would be achieved within FDA through the agency's modification of some of its existing processes.

First, BIO hopes to be able, through the user fee annual reporting mechanisms already in place, to see more clearly where there are differences among review divisions and between the two reviewing centers, the Center for Drug Evaluation and Research (CDER) and CBER, in terms of meeting the various goals of the user fee program.

Second, BIO wants to see a more structured allocation of user fee resources to activities related to review process improvements, as well as greater involvement by officials in the Office of the Commissioner in evaluating these review processes, looking for opportunities for improvements and efficiency gains, and taking steps to implement them. Therefore, we propose that a small portion of user fee resources be specifically dedicated to review process performance improvement activities and that these resources and activities be overseen by the Office of the Commissioner.

Third, we hope to improve further the level of communication between FDA and sponsors during the first review cycle. As you know, Mr. Chairman, the goal of PDUFA is for FDA to complete its review of an application in a designated period of time - six months for a so-called priority application, and ten months for a non-priority, or standard application. FDA's action on an application may be a letter to the sponsor requesting more data or information, a letter stating that the application is disapproved, or a letter stating that the application is approved. If FDA asks for more information, the sponsor generally provides the information to the agency, and then FDA enters into a second cycle of review, which can take several additional months. After this, third, fourth, and even fifth review cycles may be needed, depending on what additional information FDA requests after each of its reviews. Our review of data in FDA's reports to Congress, and information provided on the agency's web site, shows quite striking differences between the centers in regard to their ability to reach final decisions within one review cycle.

With reviews that both FDA and sponsors believe have worked well, one of the common themes we have found is early and on-going communication. Another factor that influences review processes - and, consequently, review times - is inconsistency among divisions and between centers in review practices. To address both of these factors - communication and consistency - we propose that FDA look at ways to enhance communication and to minimize inconsistency through the development, articulation, and implementation among divisions and between centers of effective review practices. We believe such sharing of good practices will go a long way to resolving differences among divisions and between the centers and will also contribute to greater efficiency of review across the board.

Finally, BIO would like to encourage FDA to use another mechanism for obtaining expert advice on cutting edge issues. BIO recognizes that biotechnology products are often novel and complex so that only a small number of research scientists and medical specialists have the expertise to understand how the products' development should proceed. Specifically, it is often the case with these products that appropriate design of the clinical trials needed for product approval is more difficult than it would be with more well-understood science. The resources CBER currently devotes to its laboratory-based, scientific studies do not address sufficiently this expertise shortage. We propose that FDA initiate a mechanism whereby an outside expert could be brought in to a meeting between the product sponsor and the FDA to assist the sponsor and the agency in deciding how best to achieve the data needed to demonstrate safety and effectiveness for the product. Such an expert would, of course, be selected by the FDA and, as is currently the case, would be screened by FDA, to ensure no conflicts of interest and no breach of the confidentiality of proprietary information. We propose that a company be provided one opportunity for such an expert consultation, so this would not become overly burdensome for the agency. As is always the case, the recommendations or views of any consultant would be advisory to the FDA, which would remain the final decision-maker.

In summary, BIO shares with FDA the goal of reauthorizing PDUFA in a way that not merely maintains but strengthens the FDA's drug and biologic review programs. We believe that the user fee program has provided, and will continue to provide, the agency the user fee resources it needs to do its work. Indeed, we propose that under PDUFA III, FDA receive a substantial infusion of new resources. But we also hope in the course of PDUFA III to achieve a better handle on review process efficiency, especially as it relates to biotechnology products, so we can look forward to even more enthusiastic support for the program reauthorization in the year 2007.

Mr. Chairman, we share the belief that timing is critical in this reauthorization process. FDA must, because of federal personnel rules, initiate a Reduction in Force (RIF) unless the agency has the legislative authority to continue providing the salaries and expenses that are derived from user fees. Notices of the possibility of such a RIF must be sent to FDA employees no later than August 1, 2002, 60 days before the end of the fiscal year and detailed plans for any RIF must be developed months earlier than that. BIO urges you, Mr. Chairman, and the Subcommittee and Committee, to act with all appropriate speed to ensure the future of this program.

Mr. Chairman, thank you for the opportunity to present BIO's views at this hearing. BIO looks forward to working with the Subcommittee and the Committee in your continuing role as the initiators and overseers of this important and highly successful program. This program has improved and even saved patients' lives, and has made the U.S. biotechnology industry the most productive in the world.

I would be happy to answer any questions you may have.