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Speech before

PhRMA Annual Meeting

Remarks by

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

April 3 , 2004

Good morning, and thank you, Miles [Miles White, PhRMA Chairman] for the kind introduction. I’d also like to thank Bob Essner for his leadership over the past year, and Alan Holmer for providing all of the energy and direction needed to help speed innovation in the U.S.

This is the first time I am addressing the pharmaceutical industry since assuming the post of Acting Commissioner of FDA, and I have to say I am glad to be with you here today to tell you about the exciting programs underway at FDA.

As you may know, I led the FDA prior to Dr. McClellan coming aboard, and it is an honor to reassume this important task. Dr. Mark McClellan was an outstanding Commissioner, and his legacy will undoubtedly be a long-lasting one. Mark helped us build a strong team, and his energy and vision motivated all of our staff.

Now Mark and I worked together on a wide variety of major agency initiatives, in particular the development of our FDA Strategic Action Plan. And as the Acting Commissioner, I would like to report that our strong plan and our dedicated team remain firmly in place, and we are continuing to execute this plan to protect and advance the public health.

We are facing more new challenges at FDA than ever before, and more new opportunities stemming from the latest biomedical innovations. And I am dedicated to making sure we are meeting these new challenges and opportunities, and helping Americans lead longer, healthier and happier lives.

One of the most pressing issues that confronts us all today – and which we’re hard at work dealing with at FDA – involves the challenges facing medical product development. This is an area that affects not only our America’s patients, but also our economy, and if addressed properly, can help ease some of the pressures that are driving up the cost of our healthcare.

This is an exciting time for the biomedical sciences, and there is a great deal of very interesting and innovative science being done in this country. Over the last few decades, the new medical breakthroughs that are being submitted to us for review at FDA have more to offer patients than ever before.

For example, new classes of drugs such as the statins are proving so beneficial to many patients with many different diseases that the introduction of these and other new drug groups perhaps rivals the introduction of penicillin.

New sciences such as genomics and proteomics might result in a new kind of medicine capable of treating the underlying causes of specific diseases in each individual patient – and perhaps even to prevent those diseases from occurring or progressing.

New engineering applications of nanotechnology can get the right treatment to the right place in each individual with far fewer side effects and complications than in the past.

And next-generation information technologies can turn the explosion of health information into far greater useful knowledge at the fingertips of doctors and patients, so that they can make far better informed, far more effective healthcare decisions than is possible today.

Now I know you’ve heard Dr. McClellan use the term “biomedical century” a number of times. And I think it’s fair to say that with so many new opportunities out there for biomedical research to transform our lives, the 21 st century does indeed hold the promise of becoming the “biomedical century.”

But the plain truth is that many of the most dramatic scientific advances that we’ve recently made in the labs haven’t yet been transformed into medical treatments for patients.

Today, there’s more spending on biomedical R&D than ever before. Total spending on biomedical research has grown exponentially over the past 10 years.

And yet, a disturbing trend is unfolding: despite the doubling of US R&D spending in both the private and public arenas, output of new products has been dropping since 1997. FDA is now receiving fewer applications for new drugs than in mid-1990’s. The number of new device applications is also decreasing.

The agency is concerned that the rate of failures also has been increasing. Almost 50% of applications are failing in late-stage Phase 3 trials. This indicates we are not succeeding in extrapolating basic science to the clinic.

And in turn, this higher failure rate is driving up the cost of successfully bringing a new drug to market. In 2003, researchers at Tufts Center for the Study of Drug Development estimated these costs to be $802 million, and some sources suggest that the total cost is closer to $1.7 billion.

This high cost of R&D is compelling companies to opt for the development of products that will recoup expenditures. This may rule out attempts to develop risky but breakthrough products or those for diseases affecting smaller populations.

And so, despite all of the wonderful innovation going on out there, the current challenges to therapeutical development are preventing us from realizing the promise of all this innovation and from converting it into medical products which directly improve the lives of patients.

Now, we recently reported that the number of truly novel drugs the FDA approved in 2003 actually increased by about 20 percent over last year, and that we saw an increase in the number of novel investigational applications we received. These are encouraging signs, and we are happy to see these slight upticks. But they are not enough.

The product development process is lengthier, more costly, and more uncertain than ever before. That means fewer products are reaching patients who desperately need them.

As you know, we’ve been taking new steps at FDA to help address this problem and improve medical innovation.

This includes various initiatives to speed review times – and as you know, FDA is committed to reducing total review time for new drugs and biologics across the board by approximately 10.5% – but it also incorporates efforts to improve the processes that researchers and manufacturers use to develop innovative products. Such efficiencies in product development will place much needed treatments in the hands of patients faster, thus helping to prevent deaths, avoid other adverse events, and improve overall health.

And we’re making good headway in various key elements of our innovation initiative.

First is the development of “quality systems” for our review procedures. The idea is to build on our professional staff expertise to identify and apply best management practices internally to our review processes. We’re moving forward in implementing these systems to make sure we are doing all we can not only to continue to reduce the time it takes to review new treatments, but also to help product developers get their applications right the first time – to do the R&D work that demonstrates safety and effectiveness as quickly and efficiently as possible. To this end, new peer review programs, coupled with more empirical data, are already enabling drug and other scientific reviewers to exchange ideas and use each others’ experience to learn about best practices.

Second, FDA is working on new guidance documents in critical medical areas. The idea here is to bring together experts in government, in academics, and in the private sector to help lay out the pathway for developing new treatments – to make sure that the clinical endpoints for studies, the study designs themselves, and the whole clinical development pathway is as clear as possible for scientists and clinicians. Over the past year, we’ve introduced new guidances on integrating pharmacogenomic testing into the drug development processes, and on investigational new drug (IND) exemptions for studies of lawfully marketed cancer drug or biological products, as well as a draft guidance for reviewers of human somatic cell therapy INDs.

We’re doing this with collaboration and new support from outside experts, including the National Institutes of Health, as well as with the help of key FDA working groups – such as our Working Groups on Obesity, Diabetes, and Oncology – which link experts from across the Agency and from the broader expert community to confront specific medical needs. One specific collaboration I’d like to point out involves our work with the National Cancer Institute. FDA and NCI are working closer than ever to help foster better and faster innovation in oncology – this joint initiative includes collaborative exchanges of expertise and resources, as well as a new system for receiving INDs electronically.

The bottom line is that FDA is interested in helping speed innovation and enhance patient safety, but we cannot do it alone. We rely on a broad range of partners to help clarify and improve the pathway for new product development.

Our efforts also include modernization of medical product manufacture. Our regulations for drug manufacturing haven’t been substantially updated in 25 years. Meanwhile, best practices in manufacturing have undergone significant progress, particularly in other high-tech industries which have adopted “six sigma” and other quality improvement methodologies.

And so, what we're doing is overhauling and upgrading a body of outdated standards and requirements called the pharmaceutical Good Manufacturing Practices. We want to make sure that our regulations encourage progress, savings and quality improvements in medicine. Our new regulatory approaches are being designed to encourage companies to continuously seek out and apply cost-reducing and precision-enhancing innovation in manufacturing and technology. This project is still ongoing, but it will be completed by the end of this summer.

In meeting our goals as outlined in PDUFA III, we’re also conducting a root cause analysis for product approvals that require more than one review cycle and many months of additional development time. Evidence shows that upfront, focused communication with product developers about FDA standards can often help the developers get the application right the first time around. We have several new pilot programs underway to pursue earlier communication with product manufacturers, and I look forward to seeing this focused communication bear fruit.

Finally, we’ve had strong success to date under the user fee program, which has reduced the median review times for regular drugs to one year, and for new molecular entitites, the most important new medicines, to six months or less.

Despite these efforts, the fact remains that in recent years, fewer new products have been making their way to patients, and the ones that do are increasingly expensive.

Two to three decades ago, the success rate for a new drug used to be about 14 percent. Today, a new medicinal compound entering Phase 1 testing -- often after more than a decade of preclinical screening and evaluation -- is estimated to have only an 8 percent chance of reaching the market. For very innovative and unproven technologies, the probability of an individual product's success is still much lower.

And so we face a real challenge today to bring the promise of 21st century medical breakthroughs to patients.

To achieve the goals of biomedical innovation and affordable health care, we are going to have to work together to find new and better ways to turn scientific discoveries into practical medical solutions that can be safely used by patients.

That means finding better ways to develop new technologies that can allow us to bring new medical products to patients faster, and more safely, and at a lower cost. It also means using the latest scientific knowledge to improve the process of developing new treatments and demonstrating that they are safe and effective and reliable.

For all that modern science has to offer, developing new treatments is still very much an art – in which hunches, and intuition, and luck play a critical role, and in which the odds are long. For medicine that is affordable and innovative, we need more well-understood science.

How can we solve this problem? Well, there are no simple answers. But one thing is becoming increasingly clear to us – that is, that 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. There are serious gaps in knowledge and antiquated product evaluation tools that create technical hurdles that relegate potential breakthrough candidates to the lab shelves.

Just two weeks ago, FDA issued a major report examining these challenges to medical development, and focusing on what we call the “critical path” to medical product development.

The “critical path” refers to the pathway that medical products must negotiate as they move from laboratory concept to actual commercialized treatments that make a real difference in patients’ lives. This encompasses not just the science of developing drugs, biologics and devices, but also the know-how for turning an experimental medicine into a finished product that can be used safely and effectively.

The thesis of our report and of this “Critical Path Research Initiative” is that much more scientific research and standards development must be devoted to improving the critical path--that investing only in basic scientific research is not enough. Specifically, the report suggests new development tools are needed to improve the predictability of the drug development process and lower the cost of research by helping industry identify product failures earlier in the clinical trials.

The white paper finds that updated development tools are needed in three critical areas: Product Safety, Medical Utility and Manufacturing. New development tools in these areas will enable better throughput to commercial product development and can act as a productivity multiplier, increasing the returns on public and private investment in basic research. By turning the critical path of product development into a fast, certain, and more affordable process, we can increase opportunities for industry competition, lower prices for consumers, and in turn improve access to better treatments for all Americans.

FDA's plan is to identify opportunities for targeted investment in research, gathering information internally and from outside stakeholders. We believe that concrete examples will crystallize support for targeted research.

With improved scientific methods and a new, shared effort by all of us, I believe we can develop and improve standards for product characterization and product safety testing, both for traditional and innovative products.

For example, applying genomic and proteomic techniques, we can develop safety assessment programs for new biomaterials. With better scientific methods, we can develop better animal models and new biomarkers for clinical safety and effectiveness.

We can apply modern engineering and cutting-edge scientific knowledge to medical product manufacturing. We can improve standardization and automation of clinical research. And we can develop novel and improved clinical trial designs and analytical methods for evaluation of safety and effectiveness.

And so I’m hopeful that as we come to together to address these issues -- to make sure we’re all using the latest scientific knowledge to improve the process of developing new treatments and demonstrating that they are safe and effective and reliable -- we can see a lot more of the biomedical progress being made in laboratories in recent years turned into safer, more effective, and more affordable treatments for patients.

It is important to point out that this initiative will complement other existing efforts to strengthen basic and translational research, for example those underway at NIH and in industry. FDA’s critical path activities and research will complement, not compete with, what our sister agencies and industry are already doing.

I’d also like to note that FDA is uniquely suited to take a major role in this effort because of our unique cross-industry and cross-cutting knowledge of the hurdles that companies and products are encountering that are causing them to fail in late stage clinical trials. The FDA has the technical expertise that can draw together stakeholders, help prioritize research that is most needed and to partner with others to conduct this research.

Issuing our report a few weeks ago was just the first step.

One of the key conclusions of our report was that collaboration is key. The FDA hopes that stakeholders – including patients, industry innovators, academics, and the financial community (those of you here today) – will read our report and help the agency prioritize actions that could break-up the log jam of products poised to enter the approval pipeline. We want to work together to ensure we are ready to evaluate breakthrough technologies.

By embarking on an aggressive, collaborative research effort, we can create a new generation of performance standards and predictive tools that will provide better answers about the safety and effectiveness of investigational products, faster and with more certainty.

Key to this effort will be the 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 technological advances, to fundamentally change and modernize the critical path for medical product testing and manufacture in the 21st Century.

FDA also intends to make internal changes and implement new collaborations to realize these priority opportunities.

This action promises not only to bring medical breakthroughs to patients more quickly, but to do so in ways that ensure greater understanding about how to maximize patient benefits and minimize their risks. Moreover, the efficiencies gained through these innovations could bring significant economies that could provide both more affordable medical products and a much greater payoff from greater predictability and speed for investment in medical research and development.

And so, I’d like to thank you again for all that you are doing to support biomedical innovation and let you know that I’m looking forward to working with you in the months ahead to bridge the gap in product development and bring new, innovative treatments from the lab to our nation’s patients to improve the public health.

Thank you.

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