News & Events

FDA Strategies for Combatting Antimicrobial Resistance

Remarks by Margaret A. Hamburg, MD
Commissioner of Food and Drugs
A One Health Colloquium
Chatham House – The Royal Institute of International Affairs
London, England
December 18, 2014


(This text provides Dr. Hamburg's prepared remarks, and it should be used with the understanding that some material may have been added or deleted during presentation.)

Thank you for that kind introduction.  It is a pleasure to join you for this important meeting. 

As some of you know, my last scheduled visit to Chatham House unfortunately was cancelled at the last minute when the U.S. Government was shut down. As of last week, I was a little nervous about this happening again, because our Congress was facing yet another potential budgetary cliff.  Luckily, they did not leap off, so I am especially glad I am here with you today.

There may be no more historically appropriate location for these meetings on antimicrobial resistance than right here in London. As most of you are aware, the initial discovery of that most emblematic of antibiotic drugs -- penicillin – was made in 1928 in this city by Alexander Fleming, a bacteriologist working at St. Mary’s Hospital.

His discovery of mold contamination on one of his staphylococcus cultures was accidental; the story goes that he had been on vacation, had inadvertently left a window open to his lab and came back to discover that his sloppiness had led to a discovery that changed the world.

Thereafter, British and American scientists, working together during World War II, pursued the therapeutic development of penicillin. And later, in the mid-1950s, an American chemist and British drug firm joined to create semisynthetic penicillins.

I offer this brief history of how penicillin was developed because it presents what I believe is an important and instructive model for our discussion of the challenge we face today, which in many ways is no less significant than that original discovery.

The path that pencillin followed from initial discovery to eventual translation into a life-saving antibacterial involved the interaction of several scientific and medical disciplines. It also owed an important debt to international collaboration, as broad organizational channels were established among nations for research and development in universities, government agencies, and industry.

Both of these factors are vital today, as we confront the challenge of increasing antibiotic resistance. 

Unfortunately, we have come to expect that antibiotics will offer an answer for practically every symptom, ailment or concern. We have used these “miracle” drugs far too indiscriminately and inappropriately --when there is no real indication and sometimes without the necessary medical or veterinary oversight. And as you know, in certain animal agriculture populations, antibiotics have come to be used even more broadly—not just to treat or control disease but to promote growth as well.

We now understand all too well that this casual behavior, including misuse and overuse, has helped those microbes adapt and survive in new and less treatable forms.

Indeed, the failure to preserve the effectiveness of current antimicrobials, as pointed out by the sobering Review on Antimicrobial Resistance report published last week, not only has enormous implications for the health of individuals as a result of the greater inability to fight infectious disease, it also will undermine many medical advances, disrupt our entire medical system, and bring with it enormous global financial cost.

The problem was by no means unforeseen. Resistance is a natural counterpart to antibiotics. As Sir Alexander Fleming himself said in 1945, “The microbes are educated to resist penicillin and a host of penicillin-fast organisms is bred out.... In such cases the thoughtless person playing with penicillin is morally responsible for the death of the man who finally succumbs to infection with the penicillin – resistant organism. I hope this evil can be averted.”

Well, it has not been averted … but it can still be meaningfully addressed. We are delineating many important strategies to do so here today. Advances in science and technology offer new opportunities to develop new antibiotics and antibiotic alternatives. Better tools aid the important task of identifying resistant organisms and track patterns of drug resistance development and spread. More responsible stewardship of these precious medical products, in human and animal populations, play a critical role in lowering resistance. And we recognize the importance—and urgency—of a sustained, committed and comprehensive response—within nations and across all nations.

In this regard, I want to take a moment to talk about some of what the U.S. government is doing, beginning with the President himself. As you may know, earlier this year President Obama gave unprecedented support for this topic through issuance of an Executive Order on Combatting Antibiotic-Resistant Bacteria, which in turn created the National Strategy on Combating Antibiotic Resistant Bacteria (CARB).

In placing such a high priority on this issue, the President recognized that fighting antibiotic resistance is both a national security priority and a public health priority – not just for our country, but every country. As the plan makes clear, to win this battle will require a multi-pronged strategy with interrelated goals that simultaneously address the many different causes for rising antibiotic resistance, and does so in the context of a broader, more integrated global effort.

At the center of this plan, as well as this conference, is the One-Health approach of combatting resistance, which offers a recognition that the health of humans is directly connected to the health of animals and to our shared environment. And it affirms that an effective response requires addressing all of these concerns together.

On the animal side, FDA has focused on addressing the non-judicious uses of antimicrobial drugs in food-producing animals.  We’ve been working to ensure that medically important antimicrobials are only used for appropriate therapeutic purposes for specific diseases, and eliminate their use for growth promotion or feed efficiency.

This has been a subject of contentious debate for a very long time, and meaningful action has been slow to come.  I am very pleased, however, that significant activities are now underway.  But it will be a dynamic, continuing process.

As many of you probably know, we recently implemented a strategy that should make a real and lasting difference in the fight against antimicrobial resistance. It has two mutually reinforcing prongs: first, to phase out the use of medically important antimicrobials in food-producing animals for production purposes such as growth promotion; and second, to bring the remaining therapeutic uses of these drugs under the oversight of veterinarians. 

Our proposal on phasing out antimicrobials for food production hinged on voluntary actions by the pharmaceutical companies. And I know that some of you questioned why we took a voluntary approach. Experience has shown us that this in fact, is the quickest, most efficient way to reach our collective goal -- considerably faster than a mandatory ban that would have required dozens of individual legal proceedings on each product and the development of specific scientific analyses of the link between that individual product’s use in animals, the development of resistance, and the impact on human disease and public health.

We’ve already seen significant progress as a result of this strategy. Every one of the 26 pharmaceutical companies that make antimicrobials for food-producing animals in our country have agreed to fully adopt the FDA’s judicious use approach.  More than 30 products already have been entirely withdrawn from the market, and labels of other drugs are being revised to remove production indications for antibiotics that are important to human medicine.

Label revision is not a token gesture. When a production indication comes off the label of an animal drug, it can no longer be marketed for that use. That medication is no longer legal. It is the same outcome as if we had banned the drug for that use.

And producers of food animals are also taking action.  For example, Perdue and Tyson, major producers of poultry in the U.S., recently announced they would no longer use antibiotics in their hatcheries.

An equally important piece of our strategy is that the remaining use of these drugs will be placed under the oversight of veterinarians. This is a significant shift, but one that makes complete sense. Available scientific evidence concerning antimicrobial resistance, including trends associated with the use of medically important antimicrobial drugs in food-producing animals, demonstrates that the judicious use of medically important antimicrobial drugs intended for use in food-producing animals should involve the expertise and accountability of a trained, licensed veterinarian.

While we’re very encouraged by these early successes, the policy is still young. We established it with a three-year time frame (the label changes are to be completed by the end of 2016). We expect additional actions in the coming months, and we will continue to take stock of the progress and consider whether further action is required. 

Efforts are also underway to devise alternatives to the use of antibiotics in agriculture for nontherapeutic uses such as growth promotion and disease prevention, an important topic here today. The recent Report to the President on Combating Antibiotic Resistance (PCAST), prepared by a distinguished outside scientific advisory committee, included a recommendation calling for the establishment by USDA of a multidisciplinary Innovation Institute and the development of a comprehensive research and development strategy for this purpose. Clearly this is an international undertaking as well.

But our work on limiting antibiotic use in food-producing animals is just one part of our comprehensive strategy. We must also foster more judicious and responsible use of antibiotics in human medicine. The earlier Chatham House meeting on AMR that I mentioned, focused on important aspects of these challenges.

We know that success will require collaborations and public-private partnerships with public health, pharmaceutical, and agricultural stakeholders to identify and carry out interventions to reduce the development and spread of antibiotic resistance -- by promoting responsible stewardship, strengthening surveillance efforts; advancing the development of innovative medical products; and improving international collaboration.

One significant component to combat emerging antibiotic resistant pathogens that very much involves the FDA is the need for robust development of new medical products -- including therapeutics to treat and cure infection, diagnostics to aid in the identification of the cause of infection and of resistant infections, and vaccines to help prevent infection with bacteria in the first place.
Ensuring a pipeline of new products will provide us with new options that we urgently need to treat patients even as we work in other ways to turn back the tide of resistant microbes.

Unfortunately, that pipeline is distressingly dry, with the development of new antimicrobials having dropped steadily since the 1980s, although recently there have been signs of renewed interest. I am pleased that we are talking a great deal about this concern here this morning.

Many factors have contributed to the decrease in new products, including the very real scientific challenges that make it more difficult to conduct studies of antibacterial drugs. Another important factor is the lack of commercial interest in antibiotic development due to the high development costs and low probability of return on investment because of limited treatment courses and sometimes the very appropriate restrictions on use.

At FDA we’ve been working in a number of ways to turn this around. We are partnering with outside groups to advance the fundamental science that underlies new product innovation and development as well as the science of clinical trials to increase their efficiency and to address overarching issues in antibiotic development, including major technical and financial barriers such as the development of endpoints for studying antibiotics in clinical trials.

I also want to underscore the importance of engaging the regulator early. We increasingly recognize that this makes a huge difference, shaping the research and development plans to make sure they are as efficient and structured as possible, with a focus on asking and answering the critical questions.

In addition, under our Generating Antibiotics Incentives Now (GAIN) law passed two years ago, FDA has been helping promote the development of new antibacterial and antifungal drugs, through a program designed to allow new antibiotics to receive quicker review and to provide early and extensive consultation with industry sponsors, including on clinical trial design. Under this law we’ve granted 64 Qualified Infectious Disease Product designations to 43 different unique molecules.  And since May of this year, we’ve approved three antibacterial drugs designated under this program. By comparison, only five new systemic antibacterial drugs were approved in the nine preceding years (2004-2013).

All of the activities I’ve discussed to this point are vital to a comprehensive strategy to overcome the spread of antibiotic resistance. But to achieve their full potential – to help us improve detection, make informed decisions, identify risk factors, and adjust our decisions in response to changes or emerging hazards relating to resistance -- we must have high quality, integrated systems of biosurveillance that can track the emergence and spread of resistant bacterial strains and their genetic profiles.

Currently we lack such a system. This means that we are forced to operate like the swordsman who fights with one hand tied behind his back. We might still win the battle, but it will take us significantly longer and who knows how many additional cuts we will endure.

To address tehse concerns, we are strengthening our current surveillance systems, such as the National Antimicrobial Resistance Monitoring System (NARMS), which was established in 1996 as a partnership between FDA, CDC and USDA to track antibiotic resistance in foodborne bacteria in humans, retail meats and food animals.

We have improved NARMS to advance automatic capture of electronic data from healthcare facilities and clinical laboratories, as well as improving the sampling of bacterial specimens from agricultural settings. NARMS is also collaborating with similar programs in other countries to work towards international harmonization of testing and reporting.

A proposal in the recent U.S. National Strategy involves the creation of a regional network of laboratories that test and report on resistant bacteria and that promotes the use of new technologies and diagnostics. Such a resource could significantly improve our ability to share the most current available data on resistance trends.

And we are working to enhance antimicrobial sales and distribution information, including developing a proposed regulation to enhance the existing requirements related to the collection of such data in food producing animals. In addition, we are working with our colleagues at USDA and CDC we to identify possible approaches for collecting information on actual antimicrobial drug use in food producing animals on the farm. Current information systems really only tell us about volume of sales but surprisingly little about actual use.

There’s one other important area of opportunity that I want to mention in the context of improved surveillance that is likely to revolutionize not just surveillance and response, but the diagnoses, treatment, and clinical management of infectious diseases.  I’m referring, of course, to the revolution in DNA sequencing. 

The new generation of technology and instrumentation has potentially enormous consequences for global health monitoring, especially if nations can agree on international standards for standardized databases for reporting an analyzing such sequence data. One promising initiative, The Global Microbial Identifier, a collaboration led by British and U.S. scientists, is helping to set standards of data quality for whole genome sequencing.

Although better data collection and analysis is a priority shared throughout the world, there is great variability in terms of progress, with some countries having established more rigorous systems for tracking resistance.

On the human side, a recent WHO report on AMR surveillance revealed a number of gaps in the systems of different countries, and pointed to the need for an improved and coordinated global effort, including wider sharing of surveillance data for public health actions and particularly for antibacterial resistance.

There are many challenges to putting such a system in place, both within individual nations and among existing surveillance networks.  The gathering of accurate information can be expensive and labor-intensive. It can be difficult to combine resistance and use data in a meaningful way. And it requires political and financial support, including recognition of the public health issues and the need for ongoing risk assessments. It also requires a coordinated research agenda that involves cooperation, good communication and data sharing and that cuts across disciplines, sectors and borders.

But there do exist a number of important programs and organizations working globally on the issue of improved surveillance, and these continue to expand.

The WHO Advisory Group on Integrated Surveillance of Antimicrobial Resistance (AGISAR), established in 2008, is doing important work in this area by promoting information-sharing on AMR.

Another important forum launched by the US in partnership with 30 other nations is the Global Health Security Agenda (GHSA), of which the first of its 11 action packages focuses on a One Health for preventing antimicrobial resistance.

The Transatlantic Task Force on Antimicrobial Resistance (TATFAR), which was established in 2009 to promote exchanges between the European Union and the United States, also offers a model for international collaboration by enabling robust technical exchanges as well as facilitating transparency and identifying best practices in the effort to collaborate and combat antibiotic resistance, including working together to coordinate clinical trials internationally. 

I also want to say a word about the importance of our working together to address the problem of substandard and counterfeit drugs. This is an increasingly significant and global concern. And too often, its contribution the development of antimicrobial resistance is under-recognized and under-addressed.But without a doubt, substandard and counterfeit products can be a significant factor in the development and spread of antibiotic resistance, as well as an enormous health hazard to those who unwittingly use them.

The significant problem of falsified and substandard antimalarial drugs, for instance, reveals the serious ripple effects that can occur. In some parts of the world, studies suggest that between 30 and 50 percent of malaria medications are substandard or counterfeit, but the overall impact of this is harder to measure. People with malaria don’t get the effective products they need, and their inadequate treatment can lead to the selection of resistant parasites, which threatens the health of communities more broadly. In addition, vital resources for medical care are wasted on ineffective products. This is a local problem, a national problem, and a global problem.

Economists, politicians, and others often talk about the economic consequences of globalization. But the challenges of this new global reality involve more than issues of commerce and trade. They relate directly to some of the most serious health problems that many nations face -- and how we in our increasingly interconnected world share ideas and solutions to these challenges.

No country today has the luxury of being able to turn inward when it comes to issues of global health, whether it involves antibiotic resistance or a disease like Ebola.  We are seeing time and again, how the transmission of antibiotic resistant strains move from the communities, clinics, and hospitals of one nation to those of many others, including, of course, those with more advanced health care systems.

It has become a truism to say that threats to health anywhere are threats to individuals everywhere. The President’s National Strategy for Combating Antibiotic-Resistant Bacteria makes this point even more succinctly -- bacteria don’t recognize borders. In short, we are all part of a global petri dish.
But I don’t want to leave you thinking that we should approach this challenge solely from a defensive posture. Although self-protection is certainly a piece of our collective response, there is a more important principle for us to uphold in the efforts we make to this end. We have the opportunity to deliver important and lasting health and economic  benefits for all.

What’s more, as doctors, veterinarians, scientists, public advocates, government officials and regulators, we have an obligation to advance the necessary strategies and approaches, whether that means creating new products or correcting the use of those we already rely on – or changing practices altogether – for both animal and human populations. We can and we must bring the best possible science to bear to achieve this end. 

In closing, I want to go back to where I began today, with the development of penicillin and how we achieved the full advantages of that medical miracle -- by working together across global boundaries and scientific disciplines.

To effectively combat the global nature of the threat of antimicrobial resistance will require our full attention and collaboration – by governments, as well as by industry, academia, and the human and animal health sectors across the globe.

There is no doubt that this group understands how high the stakes are. And you also know there is no single or easy answer to this problem. As the problem is multi-faceted, so will be the solutions.

Furthermore, you understand that this is not a question of whether we approach this from the animal side or the human side, from the perspective of developed nations or developing nations, from an emphasis on fighting resistance to existing drugs or developing new drugs. This is not a question of who or what to blame. But rather, having the will power and understanding to do what needs to be done.

Here in England, it seems most appropriate to close with a quote from Winston Churchill, who once said, “One ought never to turn one's back on a threatened danger and try to run away from it. If you do that, you will double the danger. But if you meet it promptly and without flinching, you will reduce the danger by half.”

We can overcome this challenge by working together to meet it head on -- by advancing the principle of “One Health,” with a comprehensive strategy that involves combating the growth of resistance -- while promoting responsible stewardship in both humans and animals, and developing new treatment options.
This colloquium will add new understanding, renewed commitment, and I suspect something of a blueprint for the collaborative actions needed for success. I am deeply grateful to all of you and the contributions you have made and will continue to make. And I am confident that progress will be made.

Thank you.

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