Mr. Chairman, Ranking Member Brown and Members of the Subcommittee, I am Theresa Mullin, Assistant Commissioner for Planning at the U.S. Food and Drug Administration (FDA or the Agency). I advise and assist the Commissioner concerning the performance of FDA planning, evaluation and economic analysis activities. Since the beginning of January 2003, I have been directing FDA's development of a new strategic plan and have played a lead role in coordinating the Agency's new initiative to "Improve Innovation in Medical Technology Beyond 2002." I am also Co-Chair of the National Cancer Institute (NCI)/FDA Interagency Oncology Task Force, which involves senior staff from both agencies.

We appreciate the opportunity to testify with NCI about our collaborative efforts to facilitate cancer drug development. As you may know, we are at the very beginning of this new initiative, but this is a goal that both agencies have shared. Today I will provide FDA's perspective as to why we are entering into this collaboration and what we hope to achieve.

FDA'S DRUG DEVELOPMENT PROCESS FDA's primary mission is to protect and promote the public health. One way we do this is by promptly and efficiently reviewing investigational new drug applications (INDs) for clinical studies within 30 days of submission by the product sponsor. In addition, FDA reviews new drug applications (NDAs) and biologics license applications (BLAs) and does so on an expedited basis for applications with priority status, such as those for new cancer drugs. We also monitor on-going clinical studies to ensure that subjects who volunteer for studies are protected and that the quality and integrity of scientific data are maintained. There are several phases to drug development, and FDA makes itself available to interact with product sponsors during this process (see Attachment A, Drug Development Pipeline). Meetings requested by the sponsor provide an important venue for communication. Formal meetings were established by Congress under the FDA Modernization Act of 1997, and FDA has committed to performance goals for such meetings under the Prescription Drug User Fee program. These meetings can occur from the pre-IND phase all the way to pre-NDA/BLA submission. FDA receives requests for and convenes over 1,000 such meetings with sponsors each year. Meetings with FDA can help sponsors to clarify research questions that need to be addressed, identify earlier the unsuccessful compounds, and focus research on studies of compounds that are likely to lead to approval. The Tufts Center for the Study of Drug Development has cited earlier consultation between FDA and sponsors as a key factor in reducing drug development time. Tufts estimates that shifting 5 percent of all clinical failures from Phase III/regulatory review to Phase I would reduce out-of-pocket clinical costs by up to $20 million. Upon completing and analyzing their research, sponsors, including NCI-funded researchers, send us applications providing evidence from clinical trials to demonstrate that a product is safe and effective for its intended use. We assemble a team of physicians, statisticians, chemists, biologists, microbiologists, pharmacologists, and other scientists to review the sponsor's data and proposed labeling for the drug. By setting clear standards for the evidence we need to approve a product, we try to take the guesswork out of the process and help medical researchers bring new products to American consumers more rapidly. Once a drug is approved for sale in the United States, our consumer protection mission continues. We monitor the use of marketed drugs for unexpected health risks. If new, unanticipated risks are detected after approval, we take steps to inform the public and change how a drug is used or even remove a drug from the market. We also monitor manufacturing changes to make sure they will not adversely affect safety or efficacy. We evaluate reports about suspected problems from manufacturers, health care professionals and consumers. As the pharmaceutical industry has become increasingly global, we are involved in international negotiations with other nations to harmonize standards for drug quality and the data needed to approve a new drug. This harmonization can assist in reducing the number of redundant tests manufacturers do and help ensure drug quality for consumers at home and abroad.

CURRENT STATUS OF FDA NEW DRUG APPROVALS By the end of 2002, FDA was able to meet all of the review goals for NDAs and BLAs established under the Prescription Drug User Fee Act. We evaluated many new drugs that offered important treatment options for Americans. Thanks to the enormous growth in research investments, more complex and innovative products are in development. We see this situation as one of great opportunity, and FDA is doing its part to help sponsors capitalize on the opportunities presented. However, we are concerned that the number of approvals for truly new drugs is at the lowest level in a decade, and this is directly related to the decline in the number of new applications for drugs and biologics being submitted to the Agency for approval. This trend is illustrated in the bar chart depicted in Attachment B. This pattern is occurring at the same time that the government is allocating significantly more resources to promote research, and the pharmaceutical industry has increased spending on research and development to more than $30 billion per year.

FDA MEDICAL TECHNOLOGY INITIATIVE

In January of this year, FDA launched an initiative to improve the development and availability of innovative medical products. We recognize that early communication with sponsors is essential to achieve the Agency's goal to further reduce delays and avoidable product development costs, and also to improve the quality of new product applications. With the complex new technologies in development, FDA sees an opportunity to reduce the uncertainty for product innovators, including small companies with limited experience bringing a medical technology to commercial development. We are working to clarify regulatory pathways for emerging technologies, by, for example, working to further characterize, and define the dosing for new products like cellular and gene therapies. Also, we think it would help sponsors for FDA to update current guidance and provide new ones that specify clinical endpoints, including surrogate endpoints, such as tumor shrinkage, that will provide good evidence of safety and effectiveness for new treatments for particular diseases. FDA hopes to facilitate the development of new technology by addressing and clarifying regulatory uncertainty and by increasing the predictability of product development. Some of the steps FDA is taking under its new initiative to more quickly facilitate the drug development process are listed in Attachment A.

In addition to doing what we can to help sponsors improve the quality of their data and submitted applications, the Agency is also taking steps to further improve its application review process by identifying and addressing the causes of avoidable delays in new drug review. This month we expect to publish a request for proposals to conduct both a retrospective analysis and a prospective evaluation of our review process and to provide us with ideas for possible process improvements based on comments from both FDA staff and drug sponsors.

NCI-FDA COLLABORATION

FDA is committed to finding better ways to get safe and effective treatments to patients with life-threatening diseases as quickly as possible. FDA's participation in the NCI-FDA Oncology Task Force is consistent with the Agency's initiative to improve the development and availability of innovative medical products. FDA's role is to help ensure the safety and effectiveness of drug products through the pre-market drug review process and through post-marketing programs. Through basic and clinical biomedical research and training, NCI conducts and supports programs to understand the causes of cancer; prevent, detect, diagnose, treat, and control cancer; and disseminate information to the practitioner, patient, and public. NCI's clinical research for new drug development is also subject to FDA regulation and oversight. The NCI-FDA collaboration will provide FDA with exposure to state-of-the-art technology that will enable the Agency to have a better understanding of new products in development. Similarly, NCI will benefit from hands on experience with FDA's review process that will help it to conduct and oversee research to provide evidence of safety and effectiveness, resulting in faster development of approvable products. We are hopeful that our collaborative efforts will result in better communication between reviewers and researchers, which we believe is essential to improving the development and availability of innovative medical products. Though the Task Force is in its early stages, we are considering several areas of collaboration including: joint training and fellowships; developing markers of clinical benefit, including surrogate endpoints; information technology infrastructure to better collect and share data; and ways to improve the drug development process.

Joint Training and Fellowships Staff capabilities can be enhanced through collaborative training, joint rotations, and joint appointments. We hope that bridging gaps between research and regulatory processes will make the drug development process more efficient. As noted above, early effective communication between researchers and reviewers is critical in product development. Cancer drugs are typically designated by FDA as priority review products and are eligible to be designated as "Fast Track" products. Beginning in fiscal year 2004, FDA will be piloting two programs to provide earlier FDA review and feedback for "Fast Track" products while they are still in development.

While a primary goal of the NCI/FDA collaboration is to provide cross-fertilization between the two agencies, the Task Force will also explore the possibility of a nationwide program to rotate fellows through FDA and NCI who have completed their training in medical oncology.

Developing Markers of Clinical Benefits The Medical Technology Initiative that FDA announced last January included a series of collaborative discussions with the American Society of Clinical Oncology to identify appropriate endpoints for clinical trial design for cancer therapies, by type of cancer and stage of disease. NCI is also involved in this process. These identified endpoints will be published in guidance documents. Such guidance documents, developed in collaboration with other government and academic organizations, the pharmaceutical industry, health practitioners and patients, can help sponsors structure claims, offer proven standardized approaches to evaluating efficacy, and give insights into safety testing. In NCI-FDA's Interagency Task Force discussions to date, there has been interest in further extending this work and in further identification of clinically valid surrogate endpoints.

NCI and FDA will also continue their current collaboration involving proteomics, the discovery of protein markers in the blood that can be used to detect and monitor disease course and drug response. In addition, FDA's Center for Biologic Evaluation and Research is currently collaborating with NCI on a Microarray Program for the Quality Assurance of Cancer Therapies including therapeutic cancer vaccines and other cellular and gene therapy biological products. The Microarray Program has provided a foundation for the identification of new molecular targets, understanding of the mechanism of action of targeted cancer therapeutics, and characterization of complex therapeutic cancer vaccines. As potency and identity of these cancer vaccines is difficult to assign, the genomics (study of genes)-based technology provides a novel approach to achieving this goal.

Information Technology Infrastructure FDA looks forward to collaborating with NCI building on its cancer bio-informatics infrastructure to streamline data collection, integration and analysis for pre-clinical, pre-approval, and post-approval research across all of the sectors involved in the development and delivery of cancer therapies. We are hopeful that this collaboration may ultimately reduce the reporting burden for clinical investigators and improve the quality of reported data. Some proposals being considered are: creation of a shared repository for clinical investigator Curricula Vitae (CVs) to keep current and to eliminate the requirement of repeated submissions of such CVs. Another proposal being explored is for development of templates for INDs and clinical trial protocols to simplify the process of creating and submitting these documents and improve the quality of submissions. NCI grantees may also be product sponsors that FDA regulates. Given this dual role, there may be duplicative reporting requirements that we may be able to streamline through this collaborative effort.

Improving the Drug Development Process Tufts Center for the Study of Drug Development has noted that faster development times, quicker decisions to terminate unsuccessful compounds, and higher success rates would enable industry innovators to reap substantial savings in the cost of new drug development. NCI is the sponsor of many cancer studies regulated by FDA. They too can benefit from faster development times, quicker decisions to terminate unsuccessful products, and higher success rates.

CONCLUSION

The safety and effectiveness standards for drug review and approval in the U.S. are viewed by many as the "gold standard." FDA is the recognized world leader in both the quality and speed of regulatory review. The scientists at FDA constantly strive to maintain these high standards and we believe that the new NCI-FDA Interagency Oncology Task Force will further our goals of providing new life-saving drugs to patients who need them as swiftly and cost-effectively as possible.

I am happy to answer any questions you may have.