Challenge and Opportunity on the Critical Path to New Medical Products U S Department of Health and Human Services Food and Drug Administration March 2004 INNOVATION OR STAGNATION TABLE OF CONTENTS EXECUTIVE SUMMARY i INTRODUCTION 1 INNOVATION OR STAGNATION 3 NEGOTIATING THE CRITICAL PATH 7 SCIENTIFIC AND TECHNICAL DIMENSIONS ALONG THE CRITICAL PATH 9 A BETTER PRODUCT DEVELOPMENT TOOLKIT IS URGENTLY NEEDED 11 TOOLS FOR ASSESSING SAFETY 16 Towards a Better Safety Toolkit 17 Getting to the Right Safety Standards 20 TOOLS FOR DEMONSTRATING MEDICAL UTILITY 20 Towards a Better Effectiveness Toolkit 21 Getting to the Right Effectiveness Standards 25 TOOLS FOR CHARACTERIZATION AND MANUFACTURING 25 Towards a Better Manufacturing Toolkit 27 Getting to the Right Manufacturing Standards 28 A PATH FORWARD 29 The Orphan Products Grant Program 30 The Next Steps 30 LIST OF TABLES AND FIGURES Figure 1 10 Year Trends in Biomedical Research Spending 2 Figure 2 10 Year Trends in Major Drug and Biological Product Submissions to FDA 2 Figure 3 The Escalating Cost of Development 4 Figure 4 The Critical Path for Medical Product Development 4 Figure 5 Research Support for Product Development 6 Figure 6 Working in Three Dimensions on the Critical Path 10 Figure 7 Industry FDA Interactions During Drug Development 12 Figure 8 Problem Identification and Resolution During the FDA Review Process 14 Table 1 Three Dimensions of the Critical Path 10 Executive Summary This report provides the Food and Drug Administration s FDA s analysis of the pipeline problem the recent slowdown instead of the expected acceleration in innovative medical therapies reaching patients Today s revolution in biomedical science has raised new hope for the prevention treatment and cure of serious illnesses However there is growing concern that many of the new basic science discoveries that have been made in recent years may not quickly yield more effective more affordable and safe medical products for patients This is because the current medical product1 development path is becoming increasingly challenging inefficient and costly During the last several years the number of new drug and biologic applications submitted to FDA has declined significantly the number of innovative medical device applications has also decreased The costs of product development have soared over the last decade Because of rising costs innovators concentrate their efforts on products with potentially high market return Developing products targeted for important public health needs e g counterterrorism less common diseases prevalent third world diseases prevention indications or individualized therapy is becoming increasingly challenging In fact with rising health care costs there is now concern about how the nation can continue to pay even for existing therapies If the costs and difficulties of medical product development continue to climb innovation will continue to stagnate or decline and the biomedical revolution may not deliver on its promise of better health 1 The term medical product includes drug and biological products as well as medical devices i A new product development toolkit is urgently needed to improve predictability and efficiency along the critical path What is the problem In FDA s view the applied sciences needed for medical product development have not kept pace with the tremendous advances in the basic sciences The new science is not being used to guide the technology development process in the same way that it is accelerating the technology discovery process For medical technology performance is measured in terms of product safety and effectiveness Not enough applied scientific work has been done in creating new tools to get fundamentally better answers about how the safety and effectiveness of new products can be demonstrated in faster time frames with more certainty and at lower costs As a result the vast majority of investigational products that enter clinical trials fail Often product development programs must be abandoned after extensive investment of time and resources This high failure rate drives up costs and developers are forced to use the profits from a decreasing number of successful products to subsidize a growing number of expensive failures In addition the path to market for successful candidates is long costly and inefficient due in large part to the current reliance on cumbersome assessment methods In many cases developers have no choice but to use the tools and concepts of the last century to assess this century s candidates A new product development toolkit containing powerful new scientific and technical methods such as animal or computer based predictive models biomarkers for safety and effectiveness and new clinical evaluation techniques is urgently needed to improve predictability and efficiency along the critical path from laboratory concept to commercial product We need superior development science to address these challenges to ensure that basic discoveries turn into new and better medical treatments We need to make the effort required to create better tools for developing medical technologies And we need a knowledge base built not just on ideas from biomedical research but on reliable insights into the pathway to patients The medical product development process is no longer able to keep pace with basic scientific innovation Only a concerted effort to apply the new biomedical science to medical product development will succeed in modernizing the critical path ii Many accomplished scientists in academia government and industry are working on these challenges and there has been much success in recent years But the fact remains that the pace of this development work has not kept up with the rapid advances in product discovery The result is a technological disconnect between discovery and the product development process the steps involved in turning new laboratory discoveries into treatments that are safe and effective Although the FDA is just one participant in advancing development science we have an important role to play Because FDA s standards are often used to guide development programs we need to make sure that our standard setting process is informed by the best science with the goal of promoting efficient development of safe and effective new medical treatments Because FDA is uniquely positioned to help identify the challenges to development we need to work with the larger scientific community on developing