Keynote Address, FDLI Annual Conference

Remarks at the Annual Conference of the Food and Drug Law Institute
Margaret A. Hamburg, M.D.
Commissioner of Food and Drugs
Washington, D.C.
April 24, 2012

Thank you, Geoff, for the generous introduction.

As always, I am honored and pleased to address the annual conference of the Food and Drug Law Institute. These annual meetings are important occasions, and this one especially, as you celebrate your 55th anniversary. This is a good time to reflect back a little on history…and also to look forward.

Over the years, FDLI and FDA have enjoyed a rich history of working together.  Of course, we share an interest in the nexus between science, law and public health.  But we have also developed lasting personal ties, exemplified most recently by Susan Winckler, who served as FDA’s chief of staff and is now your president and chief executive officer.

But our relationships go far back in time. In fact, I am told that the first encounter took place on November 26, 1957, and was called an "informal" conference.  FDA was represented by only five officials, including Commissioner George Larrick.  And yet, some of his opening remarks ring as true now as they did then: he described the "enormous scope" of FDA’s responsibilities, and the need for more resources and greater compliance.

I’m afraid we still have those same concerns, although our responsibilities are far broader now.

Moreover, Commissioner Larrick reported that his staff of twelve hundred oversaw regulated products worth between 60 and 70 billion dollars. Adjusted for today’s dollars, the FDA of 1957 regulated products worth approximately 490 to 570 billion dollars, which is about half the value of the goods that FDA is responsible for today.  And our staff, which now numbers over thirteen thousand, is more than ten times the size it was 55 years ago.

So some things have certainly changed.

That should come as no surprise. We live in a transforming world, and adapting to change with appropriate, smart regulation has been an essential part of our history from the very beginning. 

This ability to adapt, and to draw strength from the constantly evolving science and changing economic and cultural environment, has kept our agency relevant and successful in the pursuit of its public health mission.

And what has almost always undergirded this process—FDA’s continual, century-old evolution—has been the cyclical intersection of an urgent public health need with the legislative response to address it.

This is what has happened time and again, beginning with the passage of the Food and Drug Act of 1906 in response to muckraking reports of hazardous food and drug products in the marketplace and the horrifying depiction of conditions in the meat-packing industry in Upton Sinclair’s book, The Jungle.

Since then, a significant public health event or crisis has often served as a catalyst for Congress to give FDA additional powers to protect and promote the health of Americans. While these new authorities have not always been welcomed by industry, they have served our nation well.

It is well known that when 107 people died after a chemist used a poisonous solvent in a new liquid preparation of sulfathiozole for treating streptococcal infections, Congress enacted the Federal Food, Drug and Cosmetic Act in 1938. Among many other changes, this landmark legislation required basic safety testing of medicines.

Nay-sayers said that the new law would put countless people out of work…close plants…hurt thousands…and to quote one industry proclamation, "help none."

In fact, the 1938 reform helped millions of patients. But even with this landmark legislation, by the midpoint of the 20th century, there were still few requirements for studies to determine the actual benefits of a drug. There were no patient protections. There was little post-market scrutiny. And there was very little need for manufacturers to adhere to good manufacturing practices that would lead to consistently safe products.

Then came the outrage over the thalidomide tragedy. And fifty years ago—in 1962—Congress reacted by passing the Kefauver-Harris amendments to the Federal Food, Drug and Cosmetic Act.

To comply with the new requirements, manufacturers had to prove that a drug was not only safe, but also effective. Approvals had to be based on sound science—typically two well-controlled clinical trials. Companies had to monitor safety reports that emerged post-market and adhere to good manufacturing practices. And there were new, additional protections for patients.

Predictably, opponents said that these new provisions were unnecessary, or worse. But contrary to these pessimistic objections, I think it can be argued that the Kefauver-Harris Amendments, in fact, created the science-based FDA that exists today.

They enabled our agency to become the regulatory leader, the gold standard for the world. And, above all, they ensured that we could continue to fulfill our public health mission—protecting patients from dangers like thalidomide…while helping make safe and effective drugs available to those in need.

In the end, while the amendments clearly benefited patients, they also helped industry. They helped serve as a catalyst for innovation. Because the law not only raised scientific standards, but also helped establish a framework for a new form of scientific research enterprise.

In short, you could argue that these amendments helped usher in today’s sophisticated, science-based biotech and pharmaceutical industries.

Today we find ourselves at another critical juncture. Not, thankfully, because of a public health emergency—but because of several forces that have converged to make this a turning point.

For one, we face a set of compelling public health imperatives.  They include medical countermeasures—vaccines, diagnostics and new treatments—for potentially catastrophic biological threats, either naturally occurring or deliberately caused, and new antibiotics to address the growing problem of antibiotic resistance.

We need treatments for chronic diseases now in epidemic proportion—like type-2 diabetes mellitus, obesity, and cardiovascular disease, and devastating new disease burdens such as Alzheimer’s, that will grow with our aging population. We also need continuing efforts to find treatments and cure for rare diseases that may affect small populations, but still exact a heavy toll.

Another key factor is the enormous and unprecedented opportunities created by the remarkable advances in science and technology today—and the critical importance of translating these new findings into treatments that people need—and expect.

Globalization represents a third defining element in today’s environment, dramatically changing the world we live in but also the way our agency must operate,

I think we all recognize that this is a critical time. A critical time for our nation as we grapple with difficult economic, political, legal and social issues.

And a critical time for FDA, as we try to navigate this landscape and position ourselves to address the challenges—but seize the opportunities—of our modern world; to respond to globalization and rapid scientific advancement…and, most fundamentally, to ensure that we can fulfill our essential and unique mission to serve the public and promote and protect their health.

And this could be a landmark year for FDA–and for our nation’s health—because of several legislative proposals currently being debated by Congress.

Let me give you a brief overview of these measures that can dramatically affect FDA, the public health, and food and drug law.  I’ll start with the four user fee proposals.

Most people would agree that PDUFA, the Prescription Drug User Fee Act, stands as a successful example of cooperation among FDA, industry and Congress. In exchange for steady and predictable funding from industry user fees, FDA agreed to meet specific performance goals for its review of new drug applications.

The user fee program began in response to real problems in our drug review program, including inadequate staffing, unacceptable delays in drug review times, and a demonstrable lag of the U.S. approvals compared to other countries. And the user fee program has been working.

In the last twenty years, PDUFA has enabled FDA to provide patients with faster access to over 1,500 new drugs and biologics, including treatments for cancer, infectious diseases, neurological and psychiatric disorders, and cardiovascular diseases.

Last year, PDUFA resources helped FDA approve 35 new, groundbreaking medicines—among the highest number in recent years—including novel personalized medicine approaches and other breakthrough treatments.

In a survey released last month, the Centre for Innovation in Regulatory Science compared new drug approvals from 2002 to 2011 by FDA, the European Medical Agency (EMA) and the Japanese Pharmaceuticals and Medical Devices Agency (PMDA). For the 69 drugs approved by all three agencies, FDA’s median approval was 274 days versus 417 days for EMA, and 478 days for PMDA.  Two thirds (67%) of the 69 drugs were submitted to FDA first.

PDUFA has helped make this success possible, but enhancements proposed in PDUFA V go well beyond mere drug review performance measures. If enacted by Congress, this law will address many of the concerns raised by public representatives, the top priorities of industry, and the most important challenges within FDA.

To address the desire for increased communication and greater efficiency in the review process, we agreed to more meetings with sponsors. To aid in timely reviews and safety analyses, PDUFA V also includes a phased-in requirement for standardized, fully electronic submissions.

PDUFA V also includes a number of steps that will strengthen our capabilities and leadership in regulatory science and expedite drug development. They include developing best practices for meta-analysis, activities to enhance the use of biomarkers, exploring strategies to better utilize Patient-Reported Outcomes and other clinical endpoint assessment tools; and strengthening rare disease drug development programs and expanding post-market safety.

The implementation of all of the PDUFA V enhancements would increase the program’s user fees by approximately six percent. Overall, drug user fees would continue to pay for about 60 percent of the cost of the agency’s drug review activities.

User fees have also proven their effectiveness in the regulation of medical devices. Since the Medical Device User Fee Act of 2002 was reauthorized five years ago, FDA has approved 106 high and medium-risk devices and cleared more than 13,000 devices under the 510(k) program.

These approvals included devices that can make a difference between life and death for children—such as the first pump to support the hearts of infants to adolescents until they receive a heart transplant—and new laboratory tests, including an emergency-use diagnostic test in response to outbreak of H1N1 flu in humans.

Under an agreement worked out in February, MDUFA III would authorize FDA to collect $595 million in user fees over five years while striking a careful balance between what industry agreed to pay and what FDA will be able to accomplish with the resources provided.

Some of the notable improvements in the MDUFA III proposal would result in greater accountability, predictability, and transparency through such measures as a more structured pre-submission process and earlier interactions between FDA and applicants.

With the additional funding, the FDA would be able to hire over 200 full-time equivalent work-ers by the end of the five-year program. The FDA and industry expect that MDUFA III would result in a reduction in average total review times.

In addition to PDUFA and MDUFA, two important and historic new user fee programs are ready for Congressional action. These are for generic drugs and for biosimilars.

Designed to ease backlogs and bring more affordable drugs faster to patients, the proposed Generic Drug User Fee Act (GDUFA) would authorize the FDA to collect $299 million annually in user fees for the next five years, beginning October 1, 2012.

A key goal is to achieve a 10 month primary application review time for generic drugs, as we have for PDUFA. Currently, the median time to approval for generic applications is about 30 months, and while not all that time is attributable to FDA, we are committed to significantly reducing time to market and increasing the predictability of the review process.

GDUFA will do this while ensuring that all manufacturers who participate in the U.S. generic drug market are held to the same, consistent, high quality standards.  To achieve that, we will conduct risk-adjusted inspections of all generic active pharmaceutical ingredient and finished dosage form manufacturers on a biannual basis—with the goal of achieving parity of inspectional coverage between foreign and domestic firms by year five. 

Finally, we have proposed a user fee program under the Biologics Price Competition and Innovation Act (BPCI Act) which was enacted in 2010 as part of the Affordable Care Act. BPCI established a new abbreviated approval pathway for biological products shown to be "biosimilar to" or "interchangeable with" a licensed biological product.

Accordingly, we propose to create a new five-year program for biosimilars (BSUFA) that re-sembles PDUFA, but with some differences. For example, because there are no currently marketed biosimilars, we will charge user fees for products in development. This will generate fee revenue in the near-term and enable sponsors to have meetings with FDA early in the process of developing biosimilar biological product candidates.

Passage of these user fee bills is critical to FDA’s ability to shoulder the growing workload and harness the science necessary to address the increasingly complex products that come before us. They represent exciting and vital undertakings.

The need to reauthorize user fees, however, also provides an opportune vehicle for other FDA-related legislation. Many people believe this year’s omnibus bill will be the most significant piece of health legislation to emerge from Congress this election year. As you probably know, mark-up begins this week in both the House and Senate authorizing committees, and a number of riders are under active consideration. 

Some of them could offer a significant benefit to patients and public health by enhancing both drug and device innovation.

For example, FDA’s accelerated approval process, introduced in 1992, represents a great example of smart regulation. It has brought to the market in a more timely way more than 80 new products, including 29 cancer drugs, 32 for HIV, and 20 others for such conditions as pulmonary arterial hypertension, Fabray disease, and transfusion-dependent anemia.

But we think the accelerated approval program has been under-utilized.

We are therefore working closely with Congress to provide clarity to industry and the public—and even to FDA reviewers—so that we can approve drugs under accelerated approval for a wide variety of diseases and conditions, including rare diseases.

In addition, we have seen legislative proposals that would incorporate in law the concept of breakthrough drugs—products that demonstrate a dramatic response to therapy early in clinical trials, as was the case with the recently approved cancer drug Zalkori.

Such proposals could be helpful, by emphasizing the importance of these therapies and calling attention to pathways for expedited review and approval.

In the realm of medical devices, Congress is also considering giving a boost to an important approval pathway, the so-called "de novo" program. This is an approval program for novel medium risk devices that lack a predicate device and thus are unable to qualify for the 510(k) pathway to market.  Currently these products must first undergo the 510(k) process to determine that they are in fact "new," and only then can the review process begin. This delay seems unnecessary, and Congress is working to fix that.

This year’s omnibus bill will also seek to address one of our greatest public health challenges of the past year—drug shortages.

This is a serious, multi-faceted problem that is difficult to solve, but we’re working hard on a number of fronts.  I am proud to say that FDA prevented 195 drug shortages last year, and the pace picked up at the end of October when President Obama issued an Executive Order addressing this issue. We expanded our drug shortage team and reached out to drug manufacturers to encourage voluntary reporting of potential shortage situations.

At the same time, the Administration also indicated its support for bipartisan bills that would require the reporting of all prescription drug shortages to FDA.  While many parties, including industry, must work to prevent and manage the complex drug shortage problem, we would welcome such new tools and powers to prevent and manage drug shortages.   

To address another challenge facing FDA, Congress is grappling with the new demands of globalization. Global production of FDA-regulated products has quadrupled over the last decade and continues to grow.

Today, FDA-regulated products originate from approximately 300,000 foreign facilities spread across more than 150 countries. On the drug side, astoundingly, approximately 80% of the active pharmaceutical ingredients used in FDA-approved drugs sold in this country are manufactured outside of the United States, and 40 percent of finished drugs consumed here are manufactured elsewhere.

The complex nature of supply chains makes the task of ensuring the safety and quality of the medicines very challenging.   But consumers should have a high degree of confidence that drugs distributed through legitimate channels are safe, effective and of high quality.  So it is past time to modernize the Federal Food, Drug, and Cosmetic Act, which was enacted long before there was a truly global marketplace.

To protect Americans from unsafe pharmaceuticals in today’s globalized commerce, we need—among others—the following key authorities:

• Authority to share certain non-public information with other regulatory agencies, and to use reliable foreign audit data;
• Authority to refuse admission of products if inspection is denied; the authority to destroy unsafe drugs imported by mail; and the authority to require additional information such as unique facility identifier as condition of registration and import
• Authority to hold manufacturers accountable for the quality and origins of their raw materials, and a requirement to report to FDA threats to the drug supply chain
• Authority to require a robust system to track and trace all drugs throughout the supply chain
• Authority to require a report of incidents that could create a drug safety issue or disrupt supply

Because of the number and variety of legislative proposals now in play, this is an exciting time. But it is also a difficult and potentially risky time, not only because of current economic constraints we all face, but also because—let’s acknowledge it—there is a strong anti-government and anti-regulation sentiment among part of our public.

It is difficult to predict which road these legislative proposals will take between now and the end of September.  But whatever happens, it would be most unfortunate if newly enacted laws were to lower FDA’s high public health standards that have served patients, consumers, industry, and the public health for so long, and so well. 

They are the standards for safety and efficacy that will ensure that innovations will actually help patients. These are standards that give consumers confidence in the products in the marketplace…and these are the standards that produce medical interventions that third-party payors will choose to cover. 

I hope that, in the next several months, we will have an earnest debate about the future of the public health in the United States. Through progress on many fronts, we have reached a stage that is critical for the effective promotion and protection of the health of our citizens. 

We have a rare opportunity to move forward, toward three mutually reinforcing goals: stronger and more sophisticated regulatory science; fully transforming FDA into a modern, global public health regulatory agency; and bolstering trust and confidence in FDA decisions and work—what I call our agency’s "brand."

We’ve done much, and we are doing much more, to make these objectives a reality. We’re galvanizing numerous research partnerships to strengthen the long-neglected and underfunded field of regulatory science.

In addition to upgrading the training of our scientific staff and expanding research capacity within FDA, we have engaged in scientific collaborations with the National Institutes of Health and academic research centers; we have sponsored the creation of three Centers for Excellence in Regulatory Science based at research universities; and we are working with the Reagan-Udall Foundation to identify important regulatory science research needs and projects ripe for collaborative work.

On the global front, we are also working with our scientific and regulatory colleagues to advance regulatory science…and yesterday, we released a report on global engagement that showcases our role as a leader in improving global product safety and quality.

The report also addresses how we are implementing our global strategy, set forth in FDA’s Pathway to Global Product Safety and Quality Report, released last summer. For FDA, the distinction between domestic and global products is now obsolete, which is why last year I reorganized FDA’s critical foreign and domestic operations under a single leader.

And since coming to FDA, I have done all in my power to anchor the integrity and the "brand" of this indispensable agency in solid science—science that supports unbiased decisions based on the best available data. Unimpeachable integrity is important not only to me, but to the future of everything that FDA stands for: effective public health protection, medical product innovation, and global regulatory progress.

This morning I have focused on a few specific areas, but I would be remiss if I failed to acknowledge the excellent public health work that is going on across all the FDA centers. 

In addition to the accomplishments in biologics, drugs, and medical devices already discussed, I want to acknowledge the tremendous strides that are being made in our foods and veterinary medicine programs, as we work to put into effect the Food Safety Modernization Act and carry out our program to promote the judicious use of antibiotics.  And our tobacco program continues to meet the many ambitious milestones of its public health agenda.

But those are topics for another speech, and another day.

And so in conclusion, let me remind all of us that FDA has never stood still. Urgent needs, scientific developments and legal and legislative actions have repeatedly impelled the public health history forward, and left in its wake such luminous dates as 1906, 1938, and 1962.

We stand, again, at a critical juncture. Let us work together to make sure that the necessary steps are taken to enrich human health, medical science, and our collective future.

Thank you.