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Speech before

Global Pharmaceutical Strategies Seminar

Remarks

by

Lester M. Crawford, D.V.M., Ph.D.
Acting Commissioner of the FDA

May 25, 2004

Good afternoon, and thank you, Eran (Broshi, CEO of Ventiv Health, Inc.) for the introduction. I greatly appreciate this opportunity to discuss new strategies for an industry that makes a vital contribution to the public health, and whose success is of great importance to the Food and Drug Administration.

The development of new medical technologies is of prime interest to our government and Secretary Tommy G. Thompson who, as you undoubtedly know, last week formed a department-wide internal task force to promote new solutions to encourage innovation in health care. This is a highly significant development -- and naturally, I am not saying this because I've been appointed as the task force's chairman. Seriously, our group has been charged with improving coordination among the department's agencies and, among other tasks, greatly reduce the bureaucratic hurdles that new technologies sometimes have to overcome on their way to the market, and we intend to fulfill that mission.

As the Secretary's announcement noted, the task force efforts will build on similar endeavors at the the Food and Drug Administration and other agencies. Speaking for the FDA, in the recent years new departures, new thinking have been a way of life. Our agency is experiencing one of its great innovating periods: we're moving forward on all fronts, modernizing our rules, streamlining our procedures, and carrying out ground-breaking reforms with the goal of creating a new regulatory landscape.

The strategies we're putting to work are carefully designed to deliver optimum health gains for each tax dollar while discarding red tape and easing regulatory burden on industry. Our renovating initiatives are agency-wide, systematic, and are bringing novel approaches and fresh ideas to the regulation of all industries in FDA's purview.

In the last couple of years, for example, we've launched programs that are upgrading the quality of dietary supplements, improving the protection of patients, and strengthening the safeguards for the health of American livestock. We've even developed a comprehensive blueprint for confronting our new public health menace, the epidemic of obesity.

But there is no arena where our new concepts have been bolder and more original than in the pharmaceutical sector. In this critical segment of our public health community and national economy, we are changing a regulatory climate that has been largely dormant since the FDA's last historic achievement, which was the establishment of standards for the world's best drugs and medical devices.

Today, we are advancing toward a new seminal goal: we're creating a regulatory environment that will stimulate increased, faster, and therefore lower-cost development of needed therapies, and make them available to patients.

You know as well as I why our drug development needs to be stimulated: it fails too often. In the 1980s, the success rate for a new drug used to be about 14%. Today it is about 8%. Approximately 50% of new drugs fail to produce adequate evidence of safety and effectiveness in the late stages of the phase 3 studies, and cannot be approved. The resulting losses in revenue are raising the cost of a new drug up to $1.7 billion, a staggering sum that severely impacts on productivity. Four years ago, for example, our center for drugs received more than 130 new drug applications. Last year, the total was less than 110.

As you also know, we've been well aware of these trends and have been trying to counter them through innovation. An excellent example of FDA's creative spirit is our current overhaul of the pharmaceutical Good Manufacturing Practices, which have been unchanged in almost 25 years. The formidable and much needed purpose of this project is to ensure that our product review, compliance and inspection policies are based on cutting-edge science, and that they do not impede rapid modernization of drug manufacture.

A recent illustration of the direction and progress of this reform is a new FDA policy guide issued in response to technological progress. The new policy deals with the costly requirement for the validation of manufacturing processes for drugs before they're approved for marketing. Issued in March, this FDA guide recognizes for the first time that advanced engineering principles and control technologies can eliminate the need for the production of multiple conformance batches to ensure that the drugs will be manufactured up to standards -- in other words, that in some cases one batch can be enough.

The GMP overhaul will be completed this summer, but its benefits will continue and grow. For example, one of the initiatives we're in the process of implementing is a quality systems framework that addresses all aspects of the FDA's organizational structure, policies, methods, processes and resources in order to improve our service to the public and other stakeholders.

In addition to these undertakings, we have recently launched a series of ground-breaking programs that seek to prevent, minimize or manage the risks of the development of new drugs and biological products, activities that are crucially important for the protection and improvement of human health.

Specifically, we are advancing initiatives addressing risks that affect clinical trials; risks that are inherent in particularly challenging drugs; and risks encountered along what we call the developmental "critical path" that brings new health care products from the lab to the market.

I will now discuss the highlights of each of these groups of programs.

The first set of initiatives is focused on the shortcomings of drug applications that cannot be approved because of errors or lack of adequate evidence of their safety and effectiveness. In one of these programs, we are analyzing submissions that have failed to pass the first cycle of reviews, and had to wait for at least six months for the next review cycle and approval. The objective is to identify the root causes of these failures, and see if and how they could be avoided.

First-cycle approvals is also the goal of two three-year pilot projects we initiated last October for fast-track drugs that treat serious and life-threatening diseases. These programs, in which some of your firms are cooperating, will test whether the quality of critical submissions would be improved if our reviewers and the product sponsors engaged in either early or frequent consultations on the design and progress of the development process.

Our most recent risk-reduction effort are three draft guidances designed to improve the safety of especially risk-prone products -- drugs and biologicals (other than blood and blood components) that may require more than routine risk management. Released just three weeks ago, and entitled "Premarketing Risk Assessment," "Development and Use of Risk Minimization Action Plans," and "Good Pharmacovigilance Practices and Pharmacoepidemiologic Assessment", these documents have been developed as part of FDA's commitment under the reauthorized Prescription Drug User Fee Act of 1992.

Many of your firms are familiar with this project, and have sent us comments on the three concept papers dealing with this group of risks that were published in March 2003. The concept papers, and the stakeholders' comments, have provided the basis for the draft guidances. All three of these documents are posted on the FDA Web page.

The proposed recommendations in the guidances have a limited scope. They are non-binding, and do not impose a new burden or requirement on your manufacturers. Moreover, the suggested risk-reducing measures and tools would not be applicable to the vast majority of products, because most drug risks are adequately managed by professional labeling, package inserts or in other routine ways.

The guidances, however, describe a great variety of risk-reducing tools and measures that should be highly useful for firms whose products merit special risk-management. The recommendations range from long-range, controlled safety studies to data mining to identify a linkage between a product and adverse event, reminder systems to enhance reduced-risk prescribing and use, and performance-linked access methods from the dispensing of drugs.

Particularly valuable, I believe, is the major proposed risk-minimization tool, called RiskMAP, which is designed to meet specific risk-mitigating goals without detracting from the benefits of the product. RiskMAP is a strategic safety program suggested for such products as, for example, Schedule II controlled substances, whose benefits are important but are associated with serious risks. It can be also highly useful in helping prevent serious adverse events and/or increase the probability of important drug benefits.

The three draft guidances will be open for comment until July 6, and I urge you to let us know how to improve on them. We are especially interested in ideas on how to best characterize the types and levels of risk that might call for the use of a RiskMAP.

The most insightful and intellectually challenging of FDA's recent initiatives is a white paper, called "Challenge and Opportunity on the Critical Path to New Medical Technologies," which was issued in March. It is an analysis that probes for answers to the basic causes of the rising costs and declining success rates of new drug development in recent years.

The paper finds that the fundamental problem is "a technological disconnect" between the esoteric, cutting-edge sciences that produce pharmacological discoveries, and the much less advanced sciences applied to the subsequent development of a medical product. As a result, the processes that should convert a discovery into an approved new therapy are plagued with unforeseeable risks and uncertainties that not only frequently culminate in a product failure, but also discourage the development of medications that are important for the public health -- for instance, vaccines and therapies for counterterrorism, rare diseases, and diseases in the third world.

The way to correct this critical disparity, the white paper points out, is by greatly increasing the investment in applied science research and standards development for the processes along the critical path. Specifically, the report suggests that new tools are needed to help predict eventual product failures early in the clinical trials, and to reduce developmental uncertainties in three critical areas: the product's safety, its medical utility, and its manufacturing potential.

Sophisticated development tools in these areas can act as a productivity multiplier, increasing the returns on investment in basic research. They can lower the cost of drug development and improve medical outcomes.

I won't go into the many techniques, strategies and approaches the white paper suggests can be helpful in producing these tools. But I do want to emphasize one of the report's key conclusions, which is that collaboration is essential for success. We need to collectively embark on an aggressive, well-coordinated research to create a new generation of performance standards and predictive tools for drug development.

To that end, our agency will spearhead a collaborative development of a Critical Path Opportunities List, which will identify those areas of product development that could most benefit from innovative approaches and emerging technologies. We will make whatever internal changes may become necessary to advance this project, but we also hope for, and count on, significant input from our stakeholders -- including industry, academia, healthcare professionals, the financial community, and patients and consumers.

I have discussed the various ways in which we at the FDA are working to reduce or manage the risks that hinder the development of new health care products. This is a worthy goal not only for the Secretary's task force and our agency, but also for the members of PhRMA. We're natural allies. I am therefore looking forward to work with you in the months ahead to advance research that will make more perfect our scientific know-how, our standards and our processes. Together, we can bring more safe and effective treatments from the lab to the market, where they can benefit our patients.

Thank you.

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