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Annual Meeting Massachusetts Biotechnology Council

Margaret A. Hamburg, M.D.
Cambridge, Massachusetts
March 15, 2013

I am delighted to be here today to participate in your annual meeting. This is an impressive group, and you represent a region of the country that is absolutely vital to the advancement of biomedical product innovation.

I remember coming to meet with you in July of 2011 along with Senator Kerry….I guess I should now say Secretary Kerry. We had a lively and frank discussion as I recall. Tough at times, but useful without a doubt.

Over the last few years, we at FDA have devoted a lot of time to listening to and learning from stakeholders. It has been enormously valuable, and we have tried to be responsive to what we have heard.

I want to talk with you this morning about some of the progress that has been made, and of course what still needs to be done, together, if we are to achieve our shared goals of bringing better, safer products to people who need them…and frankly are counting on them.

No region of our country—or of the world for that matter—is doing more than this one to help leverage the opportunities in science and technology today in the service of people, their health, and their quality of life. This region, and all of you, are part of a most extraordinary life-sciences enterprise, with an R & D engine fueled by top-notch academic and industry research centers.

Here in Massachusetts you have multiple world-renowned universities and I understand the top 5 NIH funded research hospitals. So too, there are a remarkable 500 biotech and pharma companies here, and some thirty venture capital firms.

And while job growth in the biotech industry faltered during the recession, it held its own in Massachusetts so that today you employ tens of thousands of high-value workers.

This confluence of positive factors has contributed to the formation of what you call “a biotech supercluster that is second to none,” resulting in a strong record of achievement along with a robust development pipeline

But even successful biotech clusters face daunting pressures: foreign competition; rising product development costs; the challenge of securing venture capital; the looming patent cliff; uncertainties surrounding tax policy; increasingly complex reimbursement policies; and a reduction in R&D budgets -- both “Big Pharma” and government science agencies like NIH and FDA that are under the budget knife.

And these external pressures are bearing down at a critical time for biomedical innovation.

This is a golden age for biomedical research and should be so for biomedical product development. Just a few obvious examples: the sequencing of the human genome has revealed new potential drug targets; combinatorial chemistry, high throughput screening, and biosynthesis have led to thousands of candidate drugs; cutting-edge electronics, nanotechnology, and materials science have the power to transform medical devices.

And yet, despite all of this, we are not effectively translating these scientific discoveries into therapies, prevention or cures.  There is a long list of unmet needs -- emerging infections and drug resistant disease; the growing burden of chronic diseases, including obesity and diabetes; neurodegenerative conditions, the mounting problems associated with our aging population.  And the list goes on.

There is nothing I would like better than to find a single solution to all of these challenges.  But there isn’t one.  Instead, we need a comprehensive, integrated strategy that engages the full "eco-system" to advance biomedical product innovation.

As a nation, we must take a serious look at everything from intellectual property and patent policy to economic policy, including such things as access to capital, incentives, and tax policy, how we invest in science, our reimbursement policies and of course, regulatory policy and regulatory reform.

All of these area matter mightily to the robustness of the ecosystem—and they affect each other in powerful ways -- but too often they operate in silos. We are missing opportunities for synergy, and leadership, that we cannot afford to lose.

The health of the biomedical product ecosystem is so essential to our national agenda…and the impact is one of cascading benefits for all. It matters for the health of individuals and communities; it matters to the health of our health care system, with opportunities to reduce preventable costs and offering new efficiencies through meaningful care; and it matters to the health of our economy…certainly the productivity of our nation’s workforce, but also a robust biotech sector supports high value jobs, positive trade and global economic competitiveness -- factors that are particularly meaningful in today’s fiscal climate.

I am committed to working with all of you—and many others—on the broad-based national strategy to advance biomedical product innovation that I believe is so very much needed at this critical time.

I think I can say that at FDA we are striving to do our part. Success will require regulatory flexibility, advancing regulatory science, and true collaboration among health professionals, industry, government, academia, and our global health partners.

As a result of our dialogues with industry – including MassBio -- we have heard loud and clear that you want increased clarity, certainty, and predictability about FDA’s standards and expectations.

Thanks in part to these conversations, we are well aware of the challenges you face in bringing promising large and small molecule products to market, and we are trying to respond by achieving smarter regulation, greater flexibility, and creative approaches to drug development and evaluation.

Our detractors would have you believe that FDA takes a one-size fits all approach to drug development. But I hope you know, from your own experience and by looking at our recent track record of approvals, that this not the case.

We are working hard to achieve an appropriate balance between benefits and risks by offering a range of development pathways depending on the product and the disease being treated.

We recognize the need to find the most meaningful and effective ways to help speed the availability of promising new products for people in need, while never abandoning our mandate to assess safety, efficacy, and the benefit to patients. 

As evidence that we are moving in the right direction, consider the 47 novel drugs and biologics that FDA approved in 2012, the highest total in over a decade.

FDA was able to review and approve many of these new therapies quickly by communicating with drug companies early in the development process, allowing flexible clinical trial design, and using priority review and other drug approval mechanisms to expedite approval.

As a result, the majority of these important products were made available to patients in the U.S. earlier than anywhere else in the world.

A number of these 47 novel drugs and biologics approved last year were developed by Massachusetts companies.  They include Iclusig, which treats two rare forms of leukemia; the orphan drug Juxtapid; a new drug, Linzess, for irritable bowel syndrome and constipation; and the cystic fibrosis drug, Kalydeco.

Three of these four drugs were first in class molecular entities, and each has an important story to tell about how FDA is seeking to be smart and flexible regulator.

Consider Iclusig, which treats two forms of leukemia. 

Greater understanding of genetics and molecular pathways of cancer has led us from general cytotoxic agents to more targeted treatments such as Iclusig. The drug’s sponsor, ARIAD Pharmaceuticals, benefited from several of the programs FDA has in place to speed the development and review of promising drugs including:

  • fast track designation, which provides a rolling or early review of portions of the application;
  • priority review, which provides for a six-month review schedule;
  • and finally, accelerated approval, which bases approval on a surrogate endpoint or intermediate clinical endpoint, an approach which can shorten approval times and allow more rapid patient access to promising new drugs while confirmatory studies are conducted

As a result of these many programs, Iclusig was approved in a mere 2.6 months.

Many other novel drugs have been approved via one or more of these development programs. In fact, of the 39 novel drugs approved in 2012, one out of three had received fast track designation, 41 percent received priority review, and 10 percent were approved under the accelerated approval program.

Since Iclusig treats two rare forms of leukemia, it was also designated as an orphan drug, as was Juxtapid, another novel drug from a Massachusetts company, which helps treat a rare inherited condition, homozygous familial hypercholesterolemia.

Today there are treatment options for only a small percentage of the 7,000 rare diseases that collectively affect over 30 million Americans. But it is striking to recognize that one out of every three new FDA drug approvals in the past five years has been for rare diseases.

And FDA routinely approves orphan drugs based on non-traditional drug development programs.  A study published last year by the National Organization for Rare Disorders found that two-thirds of the non-cancer orphan products approved between 1983 and June 30, 2010, were based on single trials, studies using historical controls, and other strategies.

Juxtapid certainly fits that mold. It was approved based on a single clinical trial of 29 patients. And given the small number of patients studied for Juxtapid, we asked for three important post-marketing studies to collect additional safety data including a long-term patient registry.

Patients are increasingly being brought in as an important partner and resource for drug development.  I suspect that Ironwood Pharmaceuticals would agree with that.  Its drug Linzess was approved last year based in part on data collected from patient reported outcomes, which helped measure, from a patient’s point of view, treatment benefit or risk in the clinical trials.

Patient reported outcomes are a type of data the FDA is increasingly looking at, along with the patient perspective more broadly. We believe that patients can offer unique views both about their diseases and the potential gaps or limitations in available treatments in a therapeutic area. 

That’s why we’re striving for the appropriate consideration of patient perspectives in drug review, and soliciting input both on a range of issues associated with illness at different stages in drug development and on key issues at different stages of drug development.

Earlier this week I had a powerful meeting with patients and patient families to talk about what needs to be done to get innovative and life-saving medicines to them faster.  I heard, from mothers of sons with Duchenne Muscular Dystrophy, poignant but honest and important accounts of how it feels when some of their children were enrolled in trials, and some don’t qualify for inclusion.

And all of them emphasized how willing they are to work with FDA and to work with industry to ensure their sons can get the groundbreaking treatments currently under development . . . while also helping to bring both new hope and meaningful answers -- through science and clinical research -- to the next generation of patients.

Patients played a proactive role in the development of another novel drug I want to mention, Kalydeco, from the Massachusetts company Vertex. This exciting new drug targets one of the gene defects in cystic fibrosis, a serious disorder that affects the lungs and other organs.   About four per cent of those with CF, or roughly 1,200 people, are believed to have the specific defect targeted by Kalydeco.

We approved this drug in just three-and-one half months…and it is having truly amazing benefits for patients.  I think it is worth noting some of the factors that made this possible.

For one thing, the development program for Kalydeco was based on sound, truly elegant, basic and clinical science. The process reflected a true understanding of genomics of cystic fibrosis and the underlying mechanism of the disease; the targeting of their compound to a specific type of mutation; and how to design a clinical plan to demonstrate safety and effectiveness.

Vertex made good use of the opportunities for early interactions with FDA scientists.  They formulated a plan ahead of time, and carefully identified the issues they wanted to discuss.

Such early interactions can be crucial for companies. In fact, a recent evaluation by FDA showed that early interactions between a drug developer and FDA are positively correlated with early approval -- in many cases years earlier.

When Vertex was finally ready to submit an NDA, the submission package was well thought out, and FDA successfully coordinated the reviews of the many involved disciplines.

Given the robust data supporting the clinical benefit of the drug, FDA decided not to take the application to an advisory committee.  This further expedited the overall review process.

What makes Kalydeco even more remarkable is that its development was made possible in part by the Cystic Fibrosis Foundation. It paid for some of the drug development costs; it provided researchers with useful insights about the CF patient population; and it assisted in the recruitment of study participants.

The unique and mutually beneficial partnership that led to the approval of Kalydeco can serve as a model for what companies and patient groups can achieve if they collaborate on drug development.

I think these four drugs -- Iclusig, Juxtapid, Linzess and Kalydeco -- demonstrate the many ways in which FDA is striving to achieve smart, science-driven regulation. But more can be done.

Last year’s FDA Safety and Innovation Act – FDASIA – created a new expedited approval pathway for breakthrough therapy, designed for when preliminary clinical data suggest that a new drug holds real promise to offer substantial improvements over available therapies to treat a serious condition.

In addition to all of the features of fast track designation, a sponsor that receives a breakthrough designation for its drug will generally receive more intensive guidance on an efficient drug development program, beginning as early as phase 1, as well as the involvement of senior FDA management.

To date, FDA has received a total of 31 breakthrough therapy designation requests, of which nine have been granted, ten have been denied, 11 are pending, and one was withdrawn.

For those companies that are interested in knowing more about these various expedited development and review programs, we’re currently developing a guidance document that will describe each program and explain the criteria for each program -- including what we mean by such concepts as “available therapy,” “unmet medical need,” and “serious condition.” 

But companies with promising drugs need to know something else as well. It seems obvious, but it is worth underscoring, that no matter how good your data and how important the unmet need, approval also hinges on whether you have a manufacturing facility ready to go and a plan in place for scaling up production so you can manufacture your new drug and do so in a reliable, high quality facility.  Sadly, too many start-up companies fail to recognize this fundamental fact, and so approval is delayed.

I know that later today you’re scheduled to discuss another of our approval programs, our new abbreviated approval pathway for products that are biosimilar to, or interchangeable with, licensed biologicals.

Congress provided FDA with new authority in this area when it passed the 2010 Patient Protection and Affordable Care Act, and we have been working since then to put a robust program in place.  

You might expect that building a new approval program of this complexity takes much time and deliberation, and that certainly has been the case.  Last year, to help developers interested in creating biosimilar products, FDA held two public meetings issued three draft guidances to industry that set out the agency’s current thinking on key scientific and regulatory factors involved in submitting applications for biosimilar products to the agency.

We’re moving forward to finalize those guidances now.  And last month FDA issued a draft guidance on an issue common to all biologic products – how to study whether patients are at risk of having an unintended immune response to a biological product, and if they do, how to evaluate the impact of that response.

FDA has yet to receive an application for a biosimilar or interchangeable product, but we know there is much industry interest in them.  As of yesterday, FDA’s drugs center had received 51 requests for meetings on 12 different biological products; it had held 38 initial meetings with potential sponsors; and had received 15 INDs for biosimilar development programs. 

Looking ahead, FDA is also exploring with colleagues and policymakers whether a new approval mechanism might be of value for “special limited use.”  In the context of antibacterial drugs, for example, one can easily imagine the situation where it might be appropriate to approve a new drug for use in a population of patients with a serious drug-resistant infection, but limit its use in the broader population who have less severe disease and whose infections are not resistant to other antibacterial agents.

Under current requirements FDA cannot be assured that use of a product will be limited, so drug development plans must often evaluate the risks in a broader populations resulting in larger, lengthier trials.

Such an approach – which would require working with Congress for the creation of a new drug approval pathway -- could permit a more appropriate risk-benefit evaluation for conditions such as serious, drug resistant infections or a chronic disease problem like obesity, where there is a significant range of patients and associated risks.

We are exploring this new pathway because we think it could enable potentially lifesaving medicines to be made available to patients in a more timely way.

I noted at the outset that to fully translate today’s sophisticated scientific discoveries we require advancements in regulatory science -- the knowledge and tools needed to assess and evaluate a product’s safety, efficacy, quality, purity, and performance.  It involves the development of new methods, standards and models we can use to speed the development, review, approval and ongoing oversight of medical products.

To my way of thinking, it is an essential component of the scientific enterprise. Yet it has been under-appreciated, under-developed and under-funded for many years.

It is the critical link between cutting-edge discoveries and real-world diagnostics, treatments, and cures. And at this time of enormous scientific opportunity but also increasing economic constraints, investment in regulatory science will fulfill many needs.

Regulatory science can help us recognize the potential of promising therapies that might otherwise be discarded in the early stages of development . . . . . and save critical time and dollars by making sure we have the tools we need to detect – at an early stage – unsafe or ineffective therapies.

Regulatory science can help to develop and optimize innovative clinical trial designs and new analytics that can give us robust scientific answers but require smaller patient populations, shorter timeframes, and lower costs.

It can enable us to use our knowledge of biological pathways and gene variants to help identify promising new drug candidates and new potential targets for treatment . . . . . and can help usher in the era of personalized or precision medicine by linking advanced genetic data and biomarkers with targeted therapies.

Regulatory science can also bring information technology and scientific computing to bear on drug development, as well as providing such vital information as a product’s safety and benefit profile after it enters the marketplace through post-market surveillance.

Advancing regulatory science at FDA has meant strengthening our science base, including mission critical applied research; encouraging the scientific and professional development of FDA staff; and—perhaps most important, scientific collaboration.

We collaborate with outside experts in a range of formal and informal ways. A number of research consortia have proven particularly valuable and show the value of future activities – as programs as the biomarkers consortium and the Alzheimer’s neurorimagery consortium.

Also, we’ve established three Centers of Excellence in Regulatory Science and we hope to do more—one involves a set of research universities in Arkansas, one at Georgetown University and one at the University of Maryland.  These Centers are conducting targeted research, strengthening education and training in regulatory science, and bolstering scientific exchanges and collaboration. 

Maryland, for example, is forming a public private partnership – that includes industry -- to highlight awareness of regulatory science and provide insight and direction on research projects.

We are also working with the Reagan-Udall Foundation, a private and independent nonprofit research organization, on several exciting regulatory science projects.  

And late last year we joined with the industry group LifeScience Alley, academia, and nonprofit organizations to found the Medical Device Innovation Consortium, which will create a safe space for collaboration on precompetitive early stage technology efforts that will eventually benefit the entire device industry.

So I think my time is drawing to a close. I have talked some about our progress in ensuring regulatory flexibility, advancing regulatory science, and encouraging public private partnerships.  But, assuredly more still needs to be done to confront the multiple challenges of advancing biomedical product innovation. 

And for FDA, these demands come at a time of budgetary restraint, not the least of which are the sequestration of funds that has cut our budget and the need to work under the constraints of a continuing budget resolution. 

But challenges have been FDA’s constant companions since 1906, when President Teddy Roosevelt signed our agency into law.  Our agency was created with the mission to promote and protect the health of the public, and that remains our driving purpose.

But how we meet the challenges before us—how we further our work—was probably best stated by President Abraham Lincoln at an even earlier time, though admittedly in a different context.

But, in fact, the history of FDA actually begins with Lincoln, who first created the Division of Chemistry that would, decades later, evolve into the FDA.

So in the words of Lincoln “…we must rise—with the occasion. As our case is new, so must we think anew, and act anew.”

Truly, this is good advice for all of us here as we confront new challenges, but also new opportunities. As we engineer new and better ways of doing things; as we strive to develop innovative new tools and approaches. And most importantly, as we work together to develop the new treatments, prevention strategies and cures that so many people need and are counting on.

This is a mission and a responsibility that we share.

Thank you.