A Year of Significant Progress in Public Health

By: Margaret A. Hamburg, M.D.

Margaret Hamburg, M.D.A new year offers both an opportunity to look forward and an opportunity to reflect on the achievements of the previous year. And, in 2014, FDA’s accomplishments were substantial, touching on many of the agency’s broad responsibilities to protect and promote the public health.

Whether our achievements involved medical product safety and innovation, food safety and nutrition, tobacco control, or other areas of our important work, all were accomplished thanks in large part to our ability to respond to evolving needs and opportunities including the embrace of new approvals, technologies and cutting-edge science.

Consider these highlights:

Drug Approvals: This past calendar year, FDA approved 51 novel drugs and biologics (41 by CDER and 10 by CBER), the most in almost 20 years. Among CDER’s 2014 approvals are treatments for cancer, hepatitis C and type-2 diabetes, as well as the most new drugs for “orphan” diseases since Congress enacted the Orphan Drug Act over 30 years ago. Seventeen of these new approvals are “first in class” therapies, which represent new approaches in the treatment of disease. In addition, CBER approved many important biological products in 2014, including a number of groundbreaking vaccines for meningitis B, the flu, and certain types of Human Papillomavirus, the latter of which is expected to prevent approximately 90 percent of the cervical, vulvar, vaginal and anal cancers caused by HPV.

These developments are a testament not just to our expanding understanding of human biology, the biology of disease and the molecular mechanisms that drive the disease process, but also to FDA’s innovative approaches to help expedite development and review of medical products that target unmet medical needs, while adhering to the established standards for safety and efficacy. These include enhanced guidance to shape the research and development agenda, early input on clinical study needs and design, expedited review programs, targeted regulatory advice and other tools and incentives that spur investment and innovation in new medical products to address unmet medical needs.

Opioids: This past year FDA took several actions to address the abuse of opioid drugs. First, we approved abuse deterrent labeling for three opioid products that are designed to deter prescription drug abuse. These drugs used different technologies to combat the abuse problem in different ways, such as by making the product resistant to crushing or dissolving or using “aversive technology” to discourage users from taking more than the approved dosage of the drug. To help encourage the development of more drugs in abuse-deterrent forms, we are also working to provide additional advice to manufacturers. Although abuse-deterrent opioid drugs are not a silver bullet to prevent opioid abuse, we believe that our work in this area will give physicians effective new treatment options with less risk of abuse.

FDA also worked to improve the treatment of patients who overdose on opioids. We approved a new dosage form of naloxone, with an autoinjector to enable a caregiver to administer the drug in the emergency treatment of opioid overdose (as it rapidly reverses the effects of an overdose). While we continue to support development in this area, this approval offers a new valuable tool to help prevent the tragedy of opioid drug overdose.

Antibiotic Resistance: We made important strides in confronting the growing resistance of some bacteria to antimicrobial drugs. Our efforts, which are a critical part of the recently unveiled National Strategy on Combating Antibiotic Resistant Bacteria, offer a multi-pronged approach that recognizes that to effectively address this challenge means simultaneously addressing the many different causes for increasing antibiotic resistance. One important response has been efforts to expand the pipeline 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.

These efforts are already having an impact. In 2014, FDA approved four novel systemic antibiotics. In contrast, only five new antibiotics had been approved in the previous ten year period.

In addition to working on the human medical product side, we also developed and, over the next two years will be implementing, an important complementary strategy to eliminate the use of medically important antibiotics for growth promotion in food-producing animals. This strategy, once fully implemented, also will bring the remaining uses of such drugs to treat, control or prevent disease in these animals under the oversight of veterinarians. All 26 animal health companies who produce those drugs have committed to participate, and 31 products already have been withdrawn from the market.

Pharmacy Compounding: We continued to respond effectively to the 2012 outbreak of fungal meningitis that was linked to contaminated compounded drugs. This included conducting more than 90 inspections of compounding facilities across the nation in the past year. As a result, numerous firms that engaged in poor sterile practices stopped making sterile drugs, and many firms recalled drugs that have been made under substandard conditions. Where appropriate, we have worked with the Department of Justice to pursue enforcement action against some of these facilities.

We also have continued to implement the compounding provisions of the Drug Quality and Security Act (DQSA), and to develop and implement policies to address compounding by state-licensed pharmacies and the new category of registered outsourcing facilities.

Food Safety: Over the past year, the Agency has made great strides in implementing the landmark FDA Food Safety Modernization Act (FSMA). Through our proposed rules for preventive controls requirements for both human and animal food, standards for produce safety, foreign supplier verification programs, third party auditor accreditation, focused mitigation strategies to prevent intentional adulteration of food aimed at causing large-scale public health harm, and requirements for sanitary transportation practices to ensure the safe transport of food, we are working to ensure the safety of American consumers related to the foods they eat.

Nutrition: Good health depends not just on food safety, but also on what we choose to eat. FDA plays an important role in promoting good nutrition and healthy food choices by helping consumers understand the importance and benefits of good nutrition – and of being able to make informed choices about what we eat.

New rules in 2014 to finalize requiring calorie information on restaurant menus and vending machines give our citizens information they need to make healthy food choices and hopefully help reduce the epidemic of obesity in the United States. We also proposed changes to the familiar “Nutrition Facts” label on packaged foods which, when finalized, will give our citizens updated nutrition information, reflecting the most current nutrition science, to help them make healthy choices when purchasing packaged foods.

Tobacco Control: There are few areas that have as profound an impact on public health as tobacco products, which is why, five years ago, Congress gave FDA the responsibility to oversee the manufacture, marketing, distribution, and sale of tobacco products.

Over the past year, we worked with state authorities to conduct more than 124,000 inspections of retailers to enforce the ban on the sale of tobacco products to children. We unveiled the first of its kind national public education campaign—The Real Cost—to reduce youth smoking. And we took the first steps towards extending the agency’s tobacco product authority over additional products such as electronic cigarettes (e-cigarettes), cigars, pipe tobacco, nicotine gels, waterpipe (hookah) tobacco, and dissolvables not already subject to such authority through our proposed “Deeming Rule.” In addition, as part of ongoing work on product review decisions, eleven tobacco products that were allowed to enter the market during a provisional period established by the Tobacco Control Act were found “not substantially equivalent” to a predicate tobacco product. As a result of this finding, these products can no longer be sold or distributed in interstate commerce or imported into the United States.

Ebola: The tragic Ebola epidemic in West Africa demonstrates that we do not have the luxury of closing our eyes – or our borders – to the public health problems that exist in the rest of the world. I’m proud that FDA has played an important role in the response to this disease, working closely with colleagues in our government as well as the scientific community, industry and a range of other organizations and nations. We have helped facilitate the development, testing, manufacture, and availability of investigational products for use in diagnosing, treating and preventing Ebola, and worked with sponsors and health care providers to facilitate access to these products as clinical circumstances warrant. In August 2014, FDA designated the drug Z-Mapp as an orphan drug for Ebola, with the hope that this would incentivize further development and study.

And I’m very pleased to report that FDA is represented on the ground in West Africa by dedicated officers of the Commissioned Corps of the Public Health Service who continue to staff and operate the Monrovia Medical Unit in Liberia that was built to treat the health workers who became ill responding to the outbreak. Like everything FDA does, both at home and abroad, our actions on Ebola represent our agency’s continuing commitment to health and safety, and the use of science to advance these important goals.

I am extremely proud of our accomplishments in 2014, and I am confident that FDA will have a successful 2015, as we continue our work to protect and promote the public health.

Margaret A. Hamburg, M.D., is Commissioner of the Food and Drug Administration

FDA’s Take on the Executive Order and National Strategy to Combat Antibiotic-Resistant Bacteria

By: Margaret A. Hamburg, M.D.

Few issues in public health today are as critical and time urgent as combating the growing threat of antibiotic resistance. We are delighted to stand with the White House in the development and response to the President’s Executive Order and the National Combating Antibiotic-Resistant Bacteria (CARB) Strategy. Fighting antibiotic resistance is both a public health and national security priority. FDA has played a key role in the development of this important effort, and we already have made strides on many fronts to make sure that we have effective antibiotics for the future.

Margaret Hamburg, M.D.Antibiotics are precious medicines that have saved millions of lives by treating infections caused by bacteria. But their misuse, and overuse, has serious health consequences and has contributed to antibiotic resistance—in which these drugs become less effective, or ineffective, against harmful bacteria.

The consequences of antibiotic resistance must not be underestimated. With each passing day, concern mounts that more patients will have few or no therapeutic options because of resistance to available therapies. In fact, the Centers for Disease Control and Prevention (CDC) estimates that each year at least 2 million illnesses and 23,000 deaths in the United States are caused by antibiotic-resistant bacteria.

It is a high priority for FDA to work with our partners to find solutions for this serious public health problem.

To address the need for effective antibiotics, FDA is working hard to ensure development of new strategies. These include vaccines to help prevent infection with bacteria in the first place; devices to aid in the accurate diagnosis of the cause of infection and of resistant infections; and new drugs to treat patients with serious infections for whom we have few, or no, treatment options because of resistance to currently available antibiotics.

We have been engaging with outside groups to advance the science of clinical trials. For instance, we have worked with the Clinical Trials Transformation Initiative on increasing the efficiency of clinical trials; with the Engelberg Center for Health Care Reform at the Brookings Institution to address overarching issues in antibiotic development, such as the major technical and financial barriers; and with the Biomarkers Consortium of the Foundation for the National Institutes of Health (NIH) on endpoints for studying antibiotics in clinical trials. In fact, we recently joined NIH to hold a workshop to examine the technical challenges related to antibacterial product development and to discuss innovative regulatory and clinical trial approaches for bringing new products to market. (The final agenda and presentations are available online.)

FDA also has been actively implementing the Generating Antibiotics Incentives Now (GAIN) Act, a provision within the Food and Drug Administration Safety and Innovation Act (FDASIA) to promote the development of antibacterial and antifungal drugs. To date, FDA has granted 57 Qualified Infectious Disease Product (QIDP) designations under GAIN to 39 different unique molecules. Antibiotics that have a QIDP designation receive, upon request, priority review, typically shaving four months off review times, and fast track designation, which results in early consultation, including on clinical trial design, between FDA and antibiotic sponsors. QIDPs also can receive an additional five years of marketing exclusivity in addition to existing exclusivity periods at the time of approval. We’re pleased that already three QIDP designated antibacterial drugs have been approved in the past few months: Dalbavancin in May 2014, Tedizolid Phosphate in June 2014 and Oritavancin in August 2014.

Furthermore, FDA promotes the appropriate and responsible use of antibiotics in clinical medicine. Antibiotic labels contain information for health care professionals and patients on appropriate use. And we work to improve the integrity of the global supply chain for pharmaceutical products to minimize the chance of a patient receiving a substandard drug, which in some instances could promote antimicrobial resistance.

In addition, FDA has developed—and is working to implement—two strategies to ensure the judicious use of medically important antimicrobial drugs in food-producing animals. This is a vital step to better protect antibiotic effectiveness for both human and animal populations. Accordingly, we asked the manufacturers of these antibiotics used in food-producing animals to remove all growth promotion indications. Once their labels have been changed, the products can no longer be used legally for growth promotion purposes, or without veterinary oversight. We have now secured the commitment of all 26 affected animal health companies, and 31 products have been withdrawn from the market. Two other companies have implemented label changes and we will be working with the other companies to make sure that they do so as well. The second track will ensure that all remaining therapeutic uses of the affected medically important antibiotics in food-producing animals will take place under the supervision of a veterinarian. The agency continues to work under a three-year transition period, and we remain encouraged by the process.

A successful strategy to combat antibiotic-resistant bacteria will require effort and input from all involved groups, including from health care professionals and patients themselves. For our part, FDA continues to work with government partners, product developers and the scientific community as well as other critical stakeholders to address the unique and complex regulatory, scientific and policy challenges associated with this public health issue. The Executive Order and CARB strategy announced today will clearly boost our and the nation’s efforts to meet these challenges more effectively.

Margaret A. Hamburg, M.D., is Commissioner of the U.S. Food and Drug Administration

Keeping You Informed: An Update on FDA’s Judicious Use Strategy for Antimicrobial Drugs in Food-Producing Animals

By: David G. White, Ph.D.

Today, “antibiotic resistance” is a widely recognized concern. With the rise of bacteria that are resistant to many, and in some cases, all standard treatments, scientists and medical professionals are not alone in focusing on this problem. The general public is increasingly aware of the ongoing research and how antibiotic resistance can affect their immediate communities.

David WhiteAntibiotic or antimicrobial resistance is an extremely complex and challenging phenomenon that is driven by many factors. For example, bacteria can spontaneously mutate to become resistant to antimicrobials, even ones they’ve never previously been exposed to. Overuse in both humans and animals is another complicating factor. Although progress has been made in curbing inappropriate drug uses in human and veterinary medicine, more work is clearly needed.

In December 2013, FDA started the clock on major changes regarding the use of antimicrobials in food producing animals by asking the animal pharmaceutical industry to relabel certain antimicrobials used in feed in two ways: by removing those indications approved for “growth production/feed efficiency,” and by requiring veterinary oversight and involvement in order to obtain these products when they are needed to assure animal health.

We’re now six months into a three-year transition period for these actions to take place, and we’re happy to report that we’ve secured the voluntary engagement of all 26 affected animal health companies. Out of the 283 drug products, 31 have been withdrawn from the market completely, and partial label changes have been completed for two other products.

Today we released our first biannual progress report on this strategy. FDA has committed to keeping the public updated on the implementation of these changes, and we intend to release progress reports every six months. These reports will highlight changes made by drug companies to their products over the previous six months, and provide a summary of changes that are in progress.

FDA will continue to update its chart of affected applications in real time as companies make label changes.

Developing strategies for reducing antimicrobial resistance is critical for protecting both human and animal health. We are still in the early stages of implementing this part of our overall effort to slow the development of antimicrobial resistance. We’ve been working with drug companies to move this strategy forward, and we are in continual discussions with both the animal health and animal production industries to help identify the most efficient ways to make these changes to their products.

While these changes are significant steps forward, the strategy is still in its early stages. The changes are just one part of FDA’s overall strategy for monitoring and reducing antimicrobial resistance. We see these progress reports as a way to evaluate the impact of our measures on how medically important antimicrobials are used in food producing animals, but we also know there’s more work to do. Additional actions may be warranted in the future, and FDA will be continually assessing their impact to determine appropriate next steps.

As we move forward, FDA is working with federal partners, veterinary groups, and consumer advocates to develop additional ways to measure success in slowing the development of antibiotic resistance and preserving the effectiveness of existing antimicrobial drugs. As with any strategy, there will be additional challenges, but FDA remains committed to addressing them and sharing what we learn along the way.

David G. White, Ph.D., is the chief science officer and research director in FDA’s Office of Foods and Veterinary Medicine