News & Events
Increasing the Prestige of Regulatory Sciences
Remarks of Margaret A. Hamburg, M.D.
Commissioner of Food and Drugs
Society of Toxicology Annual Meeting
Tuesday, March 8, 2011
Good morning. Thank you Dr Cook for that generous introduction and for inviting me to speak at this important meeting.
Before going any further, I also want to thank all of you in the audience today—and commend you for the work you do. You spend your days finding better, more effective, more innovative ways to keep the American people—and people all over the world—safe and healthy. This is not only an essential line of work, but also a noble one…because together, you carry the solemn burden of safety. I hope that even as you immerse yourselves in the science and details of new ideas during this meeting, you keep that in mind and remember the millions of lives you impact through your work every day.
I am here today because, we too, at the FDA, grapple with issues of safety every day.
My agency is responsible for ensuring the safety, efficacy, and security of drugs, medical devices, vaccines and biological products—as well as the safety of our nation’s food supply, cosmetics, dietary supplements, animal drugs and feed, certain products that emit radiation, and most recently, tobacco products, as well. These are products that make up somewhere between 20 and 25 percent of consumer spending in the United States—and, with the notable exception of tobacco, products that the American people care about and rely on in fundamental, sometimes lifesaving, ways.
As you can see, this is an enormous, and unique, set of responsibilities. Which means that if we do not do our job, and do it completely, no one can do it for us. The FDA is a regulatory agency that takes science-based, data-driven action on behalf of the American people. All aspects of our mission are crucial to the health of individuals and the public health of our nation.
And it is science that cuts across and unites these activities and responsibilities—and always has. Since the Pure Food and Drug Act was signed into law by Teddy Roosevelt more than 100 years ago, science has helped lay a foundation for the work we do at FDA every day.
My earliest predecessor, Harvey Wiley—the very first FDA Commissioner and a chemist at the Bureau of Chemistry in the Department of Agriculture—caused a sensation with his—and I use this term lightly—"scientific" studies of adulterated food and medicines. Dr Wiley conducted human trials…but without the benefits of IRBs. He recruited a boarding house full of eager young male volunteers, to whom he fed meals full of contaminants and adulterants like borax. He then observed and documented the results.
This so-called "poison squad" of Dr. Wiley’s became quite a media phenomenon and fueled increased opposition to adulterated foods and cure-all patent medicines filled with toxins and alcohol. This combined with Upton Sinclair's turn-of-the-century exposé of the meatpacking industry, The Jungle, lead President Roosevelt to create the Bureau of Chemistry in 1906, which would later become the FDA.
Though his work would certainly not meet the rigors of scientific research today, Dr. Wiley left his mark on the agency and the country…and helped shape an agency grounded in science and driven by the pursuit of safe and healthful food and medical products. And although today’s world is very different from that of Teddy Roosevelt and Harvey Wiley, our goal remains the same: to deliver science in the service of safety and public health.
But today—in our fundamentally different and far more complex and modern environment—achieving that goal has become increasingly difficult. We are investing billions and billions of dollars in life sciences research every year. And that is essential for progress in medicine and other fields. But the truth is we are neither effectively translating these scientific discoveries into therapies nor fully applying our knowledge to ensuring the safety of food and medical products.
As we look ahead at the scientific landscape, there are so many advances that hold promise—in genomics, synthetic biology, systems biology, advanced therapies like stem cells, and emerging technologies, like nanotechnology. Yet we have not been able to fully harness the promise of this science for the benefit of people and the public health.
Of course, there are many reasons for this—and a variety of potential solutions. But I’m going to focus this morning on one very important approach that I have come to view as fundamental to progress. And that is the advancing of regulatory science—the science needed to assess and evaluate a product’s safety, efficacy, quality, and performance. It involves the development of new methods, standards, and models to speed the review, approval, and ongoing oversight of medical products and to more effectively assess safety and wholesomeness of food and other commodities.
It is an essential component of the scientific enterprise. But it has, for years, been under-appreciated, under-developed, and under-funded. And, as a result, we have been unable to apply the best possible science and technology to the tasks before us. This is simply unacceptable.
If you are talking about drugs, for example, a bench scientist may develop a new approach to a disease. A clinician may be able to show it can work. But we need regulatory science to help develop the knowledge and tools to translate discovery and innovation into those products that hold so much promise.
We cannot take full advantage of the breakneck speed of scientific discovery today unless we also emphasize innovation in regulatory science. Just as life sciences research has evolved over the past few decades, regulatory science must also evolve in important and powerful ways.
The potential is great. Advancements in regulatory science can lead to more cost-effective and timely product development and evaluation; increased capacity for post-market detection of product-associated adverse events and safety assessment; and rapid resolution of incidents involving product contamination or other concerns.
So it is more important than ever that we bring 21st-century approaches to 21st-century products and problems. And toxicology is a prime example.
As you well know, there is a great deal going on in modern toxicology today. So many of you are deeply engaged…and often working on the cutting edge.
But I think it is also fair to recognize that far too many of the toxicology tools used for regulatory assessment have relied on high-dose animal studies and default extrapolation procedures—and have remained relatively unchanged for decades, despite the scientific revolutions of the past half-century. Such testing, however, is costly and time consuming and does not always provide results that reliably correlate with human responses.
We need better predictive models to identify concerns earlier in the product development process to target efforts more effectively and to reduce time and costs—and we need to modernize the tools used to assess emerging concerns about potential risks from food and other product exposures. This requires development and validation of methods that are reliable in predicting safety and other product attributes.
Advances in life sciences and engineering are ushering in the potential to dramatically change the way toxicology assessments are performed, but these new technologies have not yet been sufficiently studied or tested. Investments today can help seed a revolutionary change in toxicology and hazard assessment going forward.
This is extremely important to our work at FDA—for both food and medical products. On all counts, we must improve methods and models to assess and effectively communicate both risks and benefits to support sound regulatory decision-making, empower consumers and, above all, protect the public health.
Which is why we’re on the verge of taking significant leaps forward in our approaches to evaluating safety. We have made "Modernizing Toxicology" one of FDA’s key scientific priorities in our emerging science and innovation strategic plan. And as part of our efforts to strengthen science at FDA, reviewers and staff throughout the agency have been—and will continue to be—educated and trained in the latest and best ways to conduct safety assessment.
Our National Center for Toxicological Research, or NCTR, remains an internationally recognized research facility that provides the agency with targeted laboratory data in support of FDA regulatory decisions. NCTR conducts research aimed at evaluating the biological effects of potentially toxic chemicals or microorganisms; defining the complex mechanisms that govern their toxicity; understanding critical biological events in the expression of toxicity; and developing methods to improve assessment of human exposure, susceptibility, and risk.
And to focus, coordinate, and further an agenda of collaborative training and science in toxicology, our Chief Scientist’s office has formed a cross-agency "Chemical and Environmental Science Council" that includes senior and junior toxicologists and regulators, and is co-chaired by Chief Scientist Dr. Jesse Goodman and NCTR Director Dr. Bill Slikker. And we view the Society of Toxicology as an important partner in this effort.
In all of these realms, we are increasingly seeing the need for strong regulatory science. Let me give you some examples.
With an advanced field of regulatory science, new tools—including functional genomics, proteomics, metabolomics, high-throughput screening, and systems biology—can replace current toxicology assays with tests that incorporate the mechanistic underpinnings of disease and of underlying toxic side effects. This would allow the development, validation, and qualification of preclinical and clinical models that accelerate the evaluation of toxicities during drug development—and replace or refine exposure experiments with predictive markers. We are working to develop biomarkers to predict toxicity and screen at-risk human subjects during clinical trials, as well as after new products are on the market.
We are also investing in analyses of large sets of data, which would provide valuable information for understanding how classes of chemicals cause toxicity. These approaches require new instrumentation, platforms, and databases, and training for FDA scientists to enable them to use and interpret data from these approaches.
Another related and important area for advancing regulatory science is to increase the use of in vitro and, potentially, computer-based modeling systems for toxicology. The development of cell lines, engineered model tissues and other cell culture approaches will be critical, not only to better understand underlying mechanisms triggered in human cells following exposure but also to replace current approaches with more efficient and cost-effective toxicology studies.
And then there are new and complex technologies, which require novel approaches and methods to better evaluate, understand, and predict the potential toxicity of these materials. In the case of nanotechnology, for example, the size of engineered nanomaterials makes many novel and innovative products possible, many of which are in the realm of FDA oversight—from drugs and medical devices, to foods, cosmetics and more. But a challenge remains with respect to more fully understanding safety…or nanotoxicology.
For example, nanomaterials can increase uptake into and between cells, which could facilitate targeted delivery of molecules to specific cells. But it may also contribute to tissue inflammation and damage. And this means that we need to develop systems to test how these novel properties impact the potential performance of nanomaterials—as well as their safety in humans.
We have a number of ongoing projects at FDA to develop this area of regulatory science, including one to characterize the nanoscale ingredients of sunscreen—zinc oxide and titanium dioxide—and assess their penetration through the skin…and another to develop screening methods for the detection of nanoscale silver in FDA-regulated products.
We also support the goal of eventually replacing whole animal testing with intelligent, integrated testing approaches that combine strategies, including computational toxicology and in vitro assays. To do this successfully, we must engage in active dialogue with our stakeholders and eventually integrate these research methods into our regulatory framework. As a first step, we have already signed onto the Tox21 initiative.
Finally, we must use regulatory science to develop new ways to protect the safety of our food supply—for example, to identify the effect of food production, processing, preparation, and use on nutrient content, toxic contaminant generation, and inactivation of naturally occurring toxins.
As you can see, the challenge is vast—and we are working hard to harness regulatory science to improve toxicology-assessment technologies and make them faster, more predictive, and better positioned to deliver approaches and products that will benefit patients and consumers.
And we can. That is the power of strategic investments in regulatory science. It can impact not just individual health but also reduce preventable health care costs and improve the effectiveness of U.S. medicine. And it can lead to better, safer and hopefully less expensive products… and new products that we want and need.
And its reach—its potential—is greater still.
There are challenging times and, understandably in this country, there is increasing focus on the need for investments that benefit the entire nation: investments that will grow our economy; that will increase high-value jobs in key sectors; that will enhance the safety and value of our exports and elevate our global economic competitiveness; and that will foster innovative products that drive economic development.
Regulatory science can help us achieve all that. But, to do so, it must be a priority for all of us and for our nation at the highest levels.
I urge you all—I ask you all—to think about the science involved in the assessment of safety and effectiveness in this more targeted way, and to help us think through the next phase of scientific progress to support innovation in these arenas. We need your help.
We at FDA are prepared—and eager—to help lead the way. But we cannot do it alone. Successfully advancing regulatory science on behalf of public health will require the exchange of ideas; it will require collaboration across the scientific community; and it will require partnerships across academia, industry, and government.
There are huge opportunities to collaborate to do more targeted problem solving research, especially in toxicology, so we can bring new methods and findings that directly apply to ensuring the safety of foods and medicines.
And only together can we advance predictive toxicology to deliver the next generation of therapies to patients and promote time and cost reductions in development that will support ongoing investment in innovation.
Fortunately, this type of work has already begun. For example, the FDA and the European Medicines Agency have recently worked to characterize novel biomarkers that identify drug-induced kidney toxicity in preclinical animal models, and several of these biomarkers have now been qualified for regulatory use.
And last year, the FDA and the U.S. National Institutes of Health launched a new NIH-FDA Regulatory Science Initiative to encourage new research in the field. Last year, we awarded our first set of grants in regulatory science—$9.4 million over 3 years to support four research projects—and we plan to make a second set of grants soon.
Resources willing, we will also continue to make targeted investments in Centers of Excellence in Regulatory Science, housed in academic settings, funded by FDA, and focused on collaborative, multidisciplinary, multi-sectoral regulatory science research.
We are hearing from researchers and clinicians that FDA and other federal agencies need to embrace a new paradigm of toxicology, one that taps into many fields of science, such as genetics, developmental biology, reproductive biology, endocrinology, to name just a few in our analyses. I fully agree with that assessment…and that call to action. But it is through collaboration that, I believe, we will best be able to do so. I encourage all of you to consider this as you continue your conversations this week.
Finally, I want to make the point that this type of extensive collaboration and partnership is particularly critical in today’s globalized world. As the world becomes smaller, and products and ideas travel seamlessly across borders and time zones, it is essential that we consider the implications of this new reality for the scientific community—and, more importantly, how to respond and how to take advantage of it.
At FDA, this has required a new way of doing business—one that takes into account the safety of imports and the security of the supply chain as we regulate food and medical products. We have expanded our programs in an effort to meet our global mandate and set up offices across the world.
And we have strengthened partnerships that promote the sharing of information and responsibilities. For example, we have increased the size of the International Scientist Exchange Program, which this year will bring together scientists from 12 different countries to share concepts, skills, and techniques required to build regulatory knowledge and infrastructure. It is interesting to note that, years ago, following an exchange program of regulatory scientists, the Korean National Research Institute of Toxicological Research was modeled after NCTR.
And this April, regulatory scientists from around the world will meet this spring for the 1st Pan Asia Conference on Food and Drug Safety Assessment in Taiwan.
All of us, regardless of nationality, share the responsibility of advancing safety research and testing—and expanding our global outreach.
And that is why meetings like this—with interesting, informed attendees and a full agenda—are so important. This is where new ideas take shape, where partnerships are formed, where old colleagues reconnect and find common ground. So I encourage you to continue talking and asking questions—and pushing each other to bring us into the new toxicology paradigm that we need in the 21st century.